Ex vivo modifiable multiple medicament final dosage form

ABSTRACT

Described embodiments include a final dosage form for administering a medicament to an animal, an article of manufacture, and method. A described final dosage form includes a dosage portion having a medicament and a release element in a first medicament-release state. The medicament has a first bioavailability to the animal. The release element is modifiable ex vivo to a second medicament-release state by an exposure to a stimulus, wherein the medicament has a second bioavailability to the animal. The final dosage form includes another dosage portion having another medicament and another release element in another first medicament-release state. In the another first medicament-release state, the another medicament has another first bioavailability to the animal. The another release element is modifiable ex vivo to another second medicament-release state by an exposure to another stimulus, wherein the another medicament has another second bioavailability to the animal.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to and claims the benefit of theearliest available effective filing date(s) from the following listedapplication(s) (the “Related Applications”) (e.g., claims earliestavailable priority dates for other than provisional patent applicationsor claims benefits under 35 USC §119(e) for provisional patentapplications, for any and all parent, grandparent, great-grandparent,etc. applications of the Related Application(s)).

RELATED APPLICATIONS

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 12/284,015, titled INDIVIDUALIZABLE DOSAGE FORM,naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde,Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L.Wood, Jr., and Victoria Y. H. Wood as inventors, filed Sep. 16, 2008,which is currently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 12/284,014, titled PERSONALIZABLE DOSAGE FORM,naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde,Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L.Wood, Jr., and Victoria Y. H. Wood as inventors, filed Sep. 16, 2008,which is currently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 12/284,013, titled MODIFIABLE DOSAGE FORM, namingMahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y.Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr.,and Victoria Y. H. Wood as inventors, filed Sep. 16, 2008, which iscurrently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 12/322,877, titled EX VIVO-MODIFIABLE PARTICLE ORPOLYMERIC BASED FINAL DOSAGE FORM, naming Mahalaxmi Gita Bangera, EdwardS. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet,Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood asinventors, filed Feb. 5, 2009, which is currently co-pending, or is anapplication of which a currently co-pending application is entitled tothe benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 12/322,874, titled MODIFYING A MEDICAMENTAVAILABILITY STATE OF A FINAL DOSAGE FORM, naming Mahalaxmi GitaBangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, DennisJ. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H.Wood as inventors, filed Feb. 5, 2009, which is currently co-pending, oris an application of which a currently co-pending application isentitled to the benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of U.S. patentapplication Ser. No. 12/322,878, titled EX VIVO ACTIVATABLE DOSAGE FORM,naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde,Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L.Wood, Jr., and Victoria Y. H. Wood as inventors, filed Feb. 5, 2009,which is currently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of United States patentapplication No. To be assigned, titled EX VIVO MODIFIABLE PARTICLE ORPOLYMERIC MEDICAMENT CARRIER, naming Mahalaxmi Gita Bangera, Edward S.Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, ElizabethA. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors,filed Apr. 29, 2009, which is currently co-pending, or is an applicationof which a currently co-pending application is entitled to the benefitof the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of United States patentapplication No. To be assigned, titled EX VIVO-MODIFIABLEMULTIPLE-RELEASE STATE FINAL DOSAGE FORM medicament carrier, namingMahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y.Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr.,and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which iscurrently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of United States patentapplication No. To be assigned, titled SYSTEM FOR EX VIVO MODIFICATIONOF MEDICAMENT RELEASE STATE, naming Mahalaxmi Gita Bangera, Edward S.Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, ElizabethA. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors,filed Apr. 29, 2009, which is currently co-pending, or is an applicationof which a currently co-pending application is entitled to the benefitof the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of United States patentapplication No. To be assigned, titled MULTIPLE CHAMBER EX VIVOADJUSTABLE-RELEASE FINAL DOSAGE FORM, naming Mahalaxmi Gita Bangera,Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet,Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood asinventors, filed Apr. 29, 2009, which is currently co-pending, or is anapplication of which a currently co-pending application is entitled tothe benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of United States patentapplication No. To be assigned, titled EX VIVO MODIFIABLE MEDICAMENTRELEASE-SITES FINAL DOSAGE FORM, naming Mahalaxmi Gita Bangera, EdwardS. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet,Elizabeth A. Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood asinventors, filed Apr. 29, 2009, which is currently co-pending, or is anapplication of which a currently co-pending application is entitled tothe benefit of the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of United States patentapplication No. To be assigned, titled EX VIVO MODIFIABLE MEDICAMENTRELEASE-ASSOCIATIONS, naming Mahalaxmi Gita Bangera, Edward S. Boyden,Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A.Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors,filed Apr. 29, 2009, which is currently co-pending, or is an applicationof which a currently co-pending application is entitled to the benefitof the filing date.

For purposes of the USPTO extra-statutory requirements, the presentapplication constitutes a continuation-in-part of United States patentapplication No. To be assigned, titled EX VIVO MODIFIABLE MEDICAMENTRELEASE-SUBSTANCE, naming Mahalaxmi Gita Bangera, Edward S. Boyden,Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A.Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors,filed Apr. 29, 2009, which is currently co-pending, or is an applicationof which a currently co-pending application is entitled to the benefitof the filing date.

The United States Patent Office (USPTO) has published a notice to theeffect that the USPTO's computer programs require that patent applicantsreference both a serial number and indicate whether an application is acontinuation or continuation-in-part. Stephen G. Kunin, Benefit ofPrior-Filed Application, USPTO Official Gazette Mar. 18, 2003, availableat http://www.uspto.gov/web/offices/com/sol/og/2003/week11/patbene.htm.The present Applicant Entity (hereinafter “Applicant”) has providedabove a specific reference to the application(s) from which priority isbeing claimed as recited by statute. Applicant understands that thestatute is unambiguous in its specific reference language and does notrequire either a serial number or any characterization, such as“continuation” or “continuation-in-part,” for claiming priority to U.S.patent applications. Notwithstanding the foregoing, Applicantunderstands that the USPTO's computer programs have certain data entryrequirements, and hence Applicant is designating the present applicationas a continuation-in-part of its parent applications as set forth above,but expressly points out that such designations are not to be construedin any way as any type of commentary or admission as to whether or notthe present application contains any new matter in addition to thematter of its parent application(s).

All subject matter of the Related Applications and of any and allparent, grandparent, great-grandparent, etc. applications of the RelatedApplications is incorporated herein by reference to the extent suchsubject matter is not inconsistent herewith.

SUMMARY

An embodiment of the subject matter described herein describes a finaldosage form for administering medicament to an animal. The final dosageform includes a dosage portion having a medicament and a release elementin a first medicament-release state. In the first medicament-releasestate, the medicament has a first bioavailability to the animal if thefinal dosage form is administered to the animal in the firstmedicament-release state. The release element is modifiable ex vivo to asecond medicament-release state by an exposure to a stimulus, whereinthe medicament has a second bioavailability to the animal if the finaldosage form is administered to the animal in the secondmedicament-release state. The final dosage form includes another dosageportion having another medicament and another release element in anotherfirst medicament-release state. In the another first medicament-releasestate, the another medicament has another first bioavailability to theanimal if the final dosage form is administered to the animal in theanother first medicament-release state. The another release element ismodifiable ex vivo to another second medicament-release state by anexposure to another stimulus, wherein the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal in the another second medicament-releasestate.

An embodiment of the subject matter described herein describes a finaldosage form for administering medicament to an animal. The final dosageform includes a dosage portion having a medicament and a release elementin a medicament-holding state. In the medicament-holding state, themedicament is substantially not bioavailable to the animal if the finaldosage form is administered to the animal in the medicament-holdingstate. The release element is modifiable ex vivo to amedicament-discharging state by an exposure to a stimulus wherein themedicament is bioavailable to the animal if the final dosage form isadministered to the animal in the medicament-discharging state. Thefinal dosage form includes another dosage portion having anothermedicament and another release element in another medicament-holdingstate. In the another medicament-holding state, the another medicamentis substantially not bioavailable to the animal if the final dosage formis administered to the animal in the another medicament-holding state.The another release element is modifiable ex vivo to anothermedicament-discharge state by an exposure to another stimulus whereinthe another medicament is bioavailable to the animal if the final dosageform is administered to the animal in the another medicament-dischargestate. In an embodiment, the final dosage form may include an outerlayer carrying the dosage portion and the another dosage portion.

An embodiment of the subject matter described herein describes a methodof modifying medicament bioavailability of a final dosage form foradministering medicament to an animal. The final dosage form includes adosage portion having a medicament and a release element in a firstmedicament-release state. In the first medicament-release state, themedicament has a first bioavailability to the animal if the final dosageform is administered to the animal in the first medicament-releasestate. The release element is modifiable ex vivo to a secondmedicament-release state by an exposure to a stimulus, wherein themedicament has a second bioavailability to the animal if the finaldosage form is administered to the animal in the secondmedicament-release state. The final dosage form includes another dosageportion having another medicament and another release element in anotherfirst medicament-release state. In another first medicament-releasestate, the another medicament has another first bioavailability to theanimal if the final dosage form is administered to the animal in theanother first medicament-release state. The another release element ismodifiable ex vivo to another second medicament-release state by anexposure to another stimulus, wherein the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal in the another second medicament-releasestate. The method includes transforming the final dosage form into aselected medicament release profile by initiating an ex vivo exposure ofthe release element or the another release element to a modificationstimulus respectfully selected from the stimulus or the anotherstimulus. In an embodiment, the method may include receiving a signalindicative of a chosen medicament bioavailability of the final dosageform. In an embodiment, the method may include selecting amedicament-release state of the release element or of the anotherrelease element in response to the chosen medicament-bioavailability ofthe final dosage form. In an embodiment, the method may includeselecting the stimulus for initiation from the stimulus or the anotherstimulus in response to the selected medicament-release state.

An embodiment of the subject matter described herein describes anarticle of manufacture. The article of manufacture includes a finaldosage form for administering medicament to an animal. The final dosageform includes a dosage portion having a medicament and a release elementin a first medicament-release state. In the first medicament-releasestate, the medicament has a first bioavailability to the animal if thefinal dosage form is administered to the animal in the firstmedicament-release state. The release element is modifiable ex vivo to asecond medicament-release state by an exposure to a stimulus, whereinthe medicament has a second bioavailability to the animal if the finaldosage form is administered to the animal in the secondmedicament-release state. The final dosage form includes another dosageportion having another medicament and another release element in anotherfirst medicament-release state. In another first medicament-releasestate, the another medicament has another first bioavailability to theanimal if the final dosage form is administered to the animal in theanother first medicament-release state. The another release element ismodifiable ex vivo to another second medicament-release state by anexposure to another stimulus, wherein the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal in the another second medicament-releasestate. The article of manufacture includes instructions specifying an exvivo exposure of the release element to the stimulus or an ex vivoexposure of the another release element to the another stimulus whichwhen implemented respectfully transform the release element to thesecond medicament-release state or the another release element to theanother second medicament-release state.

An embodiment of the subject matter described herein describes anarticle of manufacture for administering medicament to an animal. Thearticle includes a medicament. The article also includes means formedicament release control in a first state wherein the medicament has afirst bioavailability to the animal if the article of manufacture isadministered to the animal. The means for medicament release control ismodifiable ex vivo to a second state by an exposure to a stimulus,wherein the medicament has a second bioavailability to the animal if thearticle of manufacture is administered to the animal. The articleincludes another medicament. The article also includes another means formedicament release control in another first state wherein the anothermedicament has another first bioavailability to the animal if thearticle of manufacture is administered to the animal. The another meansfor medicament release control is modifiable ex vivo to another secondstate by an exposure to another stimulus, wherein the another medicamenthas another second bioavailability to the animal if the article ofmanufacture is administered to the animal.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an example environment that includes an animal, across-sectional view of an example final dosage form for administering amedicament to the animal, and an example stimulation source operable toemit a stimulus;

FIG. 2 illustrates another example environment that includes the animal,a cross-sectional view of an example final dosage form for administeringa medicament to the animal, and the example stimulation source operableto emit the stimulus;

FIG. 3 illustrates a further example environment that includes theanimal, a cross-sectional view of an example final dosage form foradministering a medicament to the animal, and the example stimulationsource operable to emit the stimulus;

FIG. 4 illustrates another example environment that includes the animal,a cross-sectional view of an example final dosage form for administeringa medicament to the animal, and the example stimulation source operableto emit the stimulus;

FIG. 5 illustrates a further example environment that includes ananimal, a cross-sectional view of an example final dosage form fortransporting medicament to the animal;

FIG. 6 illustrates an example environment that includes an article ofmanufacture;

FIG. 7 illustrates an example operational flow modulating amedicament-release characteristic of a final dosage form;

FIG. 8 illustrates an alternative embodiment of the operational flow ofFIG. 7;

FIG. 9 illustrates an example operational flow fulfilling a requestspecifying a dose of a medicament for an individual animal;

FIG. 10 illustrates an alternative embodiment of the example operationalflow of FIG. 9;

FIG. 11 illustrates another alternative embodiment of the exampleoperational flow of FIG. 9

FIG. 12 illustrates a further embodiment of the example operation ofFIG. 9;

FIG. 13 illustrates another embodiment of the example operational flowof FIG. 9;

FIG. 14 illustrates a further embodiment of the example operational flowof FIG. 9.

FIG. 15 illustrates an example environment that includes an animal, across-sectional view of an example final dosage form for administeringthe medicament to the animal, and the example stimulation sourceoperable to emit a stimulus;

FIG. 16 illustrates an example environment that illustrates a finaldosage form having a release element implemented by a characteristicresponse of a particle or a polymer to the stimulus;

FIG. 17 illustrates an example environment that includes an article;

FIG. 18 illustrates an example operational flow modifying a medicamentavailability characteristic of a final dosage form;

FIG. 19 illustrates an example final dosage form for administering amedicament to an animal;

FIG. 20 illustrates an example environment that includes a final dosageform 1502 configurable to administer a medicament to an animal;

FIG. 21 illustrates an example environment depicting retention andrelease states of particle or polymeric material (depicted as ahydrogel) responsive to an ex vivo stimulus;

FIG. 22 illustrates an example environment that includes an article ofmanufacture;

FIG. 23 illustrates an example environment that includes a final dosageform for administering the medicament to an animal;

FIG. 24 illustrates an example environment that includes a final dosageform and an operational flow;

FIG. 25 illustrates alternative embodiments of the activation operationof FIG. 24;

FIG. 26 illustrates an example embodiment of a final dosage form foradministering a medicament;

FIG. 27 illustrates an example system in which embodiments may beimplemented;

FIG. 28 illustrates an example environment that includes a final dosageform for administering the medicament to an animal;

FIG. 29 illustrates an example environment that includes a final dosageform for administering the medicament to an animal;

FIG. 30 illustrates an example environment that includes a final dosageform and an operational flow;

FIG. 31 illustrates an example article of manufacture for administeringmedicament to an animal;

FIG. 32 illustrates an example environment that includes a final dosageform for administering medicament to an animal;

FIG. 33 illustrates an example environment that includes an article ofmanufacture;

FIG. 34 illustrates an example environment that includes a final dosageform and an operational flow;

FIG. 35 illustrates an alternative embodiment of the individualizationoperation of FIG. 34;

FIG. 36 illustrates an alternative embodiment of the individualizationoperation of FIG. 34;

FIG. 37 illustrates an alternative embodiment of the operational flow ofFIG. 34;

FIG. 38 illustrates an example environment that includes a final dosageform and an operational flow;

FIG. 39 illustrates an example vehicle for administering a medicament toan animal;

FIG. 40 illustrates an example system;

FIG. 41 illustrates an example environment;

FIG. 42 illustrates an example environment that includes a final dosageform for administering medicament to an animal;

FIG. 43 illustrates an example environment that includes a final dosageform and an operational flow;

FIG. 44 illustrates an alternative embodiment of the operational flow ofFIG. 43;

FIG. 45 illustrates an example environment that includes an article ofmanufacture;

FIG. 46 illustrates an example article of manufacture for administeringmedicament to an animal;

FIG. 47 illustrates an environment that includes a final dosage form foradministering medicament to an animal;

FIG. 48 illustrates an example environment that includes a final dosageform for administering medicament to an animal;

FIG. 49 illustrates an example environment that includes a final dosageform and an operational flow;

FIG. 50 illustrates an example alternative embodiment of the operationalflow of FIG. 49;

FIG. 51 illustrates an example environment that includes an article ofmanufacture 4001;

FIG. 52 illustrates an example environment that includes an article ofmanufacture;

FIG. 53 illustrates an example article of manufacture for administeringmedicament to an animal;

FIG. 54 illustrates an example environment that includes a final dosageform for administering medicament to an animal;

FIG. 55 illustrates an example environment that includes a final dosageform and an operational flow;

FIG. 56 illustrates an alternative embodiment of the operational flowdescribed in FIG. 55;

FIG. 57 illustrates an example environment;

FIG. 58 illustrates an example article of manufacture for administeringmedicament to an animal;

FIG. 59 illustrates an example environment that includes a final dosageform for administering medicament to an animal;

FIG. 60 illustrates an example environment that includes a final dosageform for administering medicament to an animal and an operational flow;

FIG. 61 illustrates an alternative embodiment of the operational flowdescribed in conjunction with FIG. 60;

FIG. 62 illustrates an example article of manufacture for administeringmedicament to an animal;

FIG. 63 illustrates an example environment that includes a final dosageform for administering medicament to an animal;

FIG. 64 illustrates an example environment that includes a final dosageform for administering medicament to an animal;

FIG. 65 illustrates an example environment that includes a final dosageform and an operational flow;

FIG. 66 illustrates an alternative embodiment of the operational flowdescribed in conjunction with FIG. 65; and

FIG. 67 illustrates an example article of manufacture for administeringmedicament to an animal.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrated embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented here.

FIG. 1 illustrates an environment 100 that includes an animal 198, across-sectional view of an example final dosage form 102 foradministering the medicament 190 to an animal, such as the animal 198,and an example stimulus source 194 configured to emit a stimulus 192. Inan embodiment, the final dosage form includes a dosage form havingcompleted a manufacturing or production process. In an embodiment, thefinal dosage form includes a product, finished tablet, or capsule readyfor distribution to a hospital, pharmacy, or retail store forindividualizing to a particular animal, such as the animal 198. In anembodiment, the final dosage form includes a tablet shape, a sphericalshape, or an ellipsoidal shape. In an embodiment, the final dosage formincludes a structure or a particle carryable or transportable by aliquid or other fluid carrier.

In an embodiment, the animal 198 includes any living being capable ofvoluntary movement and possessing specialized sense organs. In anembodiment, the animal includes a human. In an embodiment, the animalincludes a mammal. In an embodiment, administering, administration, oradminister the medicament to the animal includes give or apply themedicament 190 to the animal. In an embodiment, administering themedicament to the animal includes dispensing the medicament to theanimal. In an embodiment, administering the medicament to the animalincludes delivering the medicament to the animal. In an embodiment,administering the medicament to the animal includes directly orindirectly injecting the medicament to the animal. In an embodiment,administering the medicament to the animal includes applying themedicament to the animal. In an embodiment, administering the medicamentto the animal includes providing the medicament to the animal.

The final dosage form 102 includes an outer layer 110, a release element130, and a chamber 120. The release element 130 is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to a stimulus. For example, thestimulus may include the stimulus 192. The chamber 120 includes achamber wall 122, which is substantially within the outer layer 110, andis configured to carry the medicament 190. In an embodiment, the finaldosage form 102 includes an intermediate outer layer (not shown) withthe release element interposed between the outer layer and theintermediate outer layer, and the chamber is substantially within theintermediate outer layer (not shown).

In an embodiment, the outer layer 110 of the final dosage form 102includes an outer layer of at least one of a tablet, capsule, particle,or solid final dosage form. In an embodiment, the outer layer 110includes an outer peripheral layer. FIG. 1 illustrates an exampleembodiment where the outer layer 110 includes an outer layer around thechamber wall 122 and the release element 130. In an embodiment, theouter layer 110 is configured for administration to the animal 198 by atleast one of an oral, enteral, inhalation, or implant route. In anembodiment, an enteral route includes a rectal route, or a vaginalroute, such as by a suppository. In an embodiment, the outer layer isconfigured for administration to the animal by at least one ofparenteral, nasal, auditory canal, pulmonary, topical, or subdermalroute.

In an embodiment, the outer layer 110 includes an outer layer configuredto release the medicament in an in vivo environment of the animal. In anembodiment, the outer layer 110 includes an outer surface. In anembodiment, the outer layer includes an outer surface of a biocompatiblemedicament administration vehicle or transport.

In an embodiment, the outer layer 110 of the final dosage form 102includes an erodible outer layer. Formulations of erodible dosage formsare known in the art. In an embodiment, the erodible outer layerincludes an erodible outer layer that is at least one of soluble,permeable, or disintegrable within the animal 198. In an embodiment, theerodible outer layer includes an erodible outer layer having at least aportion that is at least one of soluble, permeable, or disintegrable inresponse to an acidic environment within the animal. In an embodiment,the erodible outer layer includes an erodible outer layer having atleast a portion that is at least one of soluble, permeable, ordisintegrable in response to a pH neutral or a basic environment withinthe animal.

In an embodiment, the outer layer 110 of the final dosage form 102includes an outer portion of a plurality of particles. Examples of sucha particle include one or more of hydrogels, microspheres, polymericmicrospheres, and nanoparticles as described in Lin et al., Hydrogels incontrolled release formulations: Network design and mathematicalmodeling, A DVANCED DRUG DELIVERY REVIEWS 58 (2006) (1379-1408). In anembodiment, the outer layer 110 of the final dosage form 102 includes anouter portion of an aggregation of molecules. An embodiment includes anouter layer 110 configured to allow an in vivo discharge of at least aportion of the medicament 190 from the chamber 120 after an exposure ofthe release element 130 to the stimulus 192. An embodiment includes anouter layer 110 configured in cooperation with the release element 130to allow an in vivo discharge of at least a portion of the medicament190 from the chamber 120 after an exposure of the release element 130 tothe stimulus. In an embodiment, the outer layer 110 includes an outerlayer of at least a portion of the release element. In an embodiment,the release element forms the outer layer. An embodiment includes anouter layer configured to contain the medicament until the final dosageform is administered into the animal.

In an embodiment of the release element 130, the firstmedicament-release state is configured to retard medicament release invivo and the second medicament-release state is configured to allowmedicament release in vivo. In an embodiment of the release element 130,the first medicament-release state is configured to allow medicamentrelease in vivo and the second medicament-release state is configured toretard medicament release in vivo.

FIG. 1 illustrates a release element 130 disposed within the outer layer110. In an embodiment, the release element includes a release elementthat is at least partially disposed within the outer layer, or a releaseelement that is not disposed within the outer layer. For example, FIG. 2infra, illustrates an example of a final dosage form 202 that includes arelease element 230 that is not disposed within the outer layer 210.FIG. 3, infra, illustrates an example of a final dosage form 302 thatincludes a release element 330 disposed at least partially within theouter layer 310.

Returning to FIG. 1, in an embodiment, a release element 130 may beconfigured in a first medicament-release state and modifiable ex vivo toa second medicament-release state by an exposure to the stimulus 192. Anembodiment includes a release element configured in a firstmedicament-release state and reconfigurable to a secondmedicament-release state by an exposure to the stimulus.

In an embodiment, the release element 130 includes a release elementconfigured in a first medicament-release state and modifiable ex vivo toa second medicament-release state by an exposure to a non-ionizingradiation, illustrated as the stimulus 192. In an embodiment, therelease element 130 is configured in a first medicament-release stateand modifiable ex vivo to a second medicament-release state by anexposure to an electromagnetic radiation, illustrated as the stimulus192. In an embodiment, the release element 130 is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to a light radiation, alsoillustrated as the stimulus 192. For example, light radiation mayinclude at least one of the spectrum of ultraviolet (UV), visible light,/or infrared (IR).

In an embodiment, the release element 130 includes, but is not limitedto, at least one of a poly(vinyl alcohol), gel, gel matrix, hydrogel, orazopolymer membrane. For example, a poly(vinyl alcohol) is described in(S. P. Vijayalakshmi, et al., Photodegradation of poly(vinyl alcohol)under UV and pulsed-laser irradiation in aqueous solution, JOURNAL OFAPPLIED POLYMER SCIENCE, Vol. 102, No. 2, 958-966, 2006). For example,photo responsive polymers, including using an azopolymer with laserholography to generate the gated layer, are described in (J. Kyoo Lee,et. al., Photo-Triggering of the Membrane Gates in Photo-ResponsivePolymer for Drug Release, ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY,(27th Annual International Conference) 2005 Pages: 5069-5072 (2005). Inan embodiment, the release element includes a photo-labile bond betweena molecule of the medicament 190 and a bioactivity inhibiting moleculethat is configured in a first medicament-release state and modifiable exvivo to a second medicament-release state by an exposure of the labilebond to the stimulus. Examples of such a photo-labile bond are describedin M. Scwarcznski, et al., Development of first photo responsive prodrugof paclitaxel, 16 BIOORGANIC & MEDICAL CHEMISTRY LETTERS, Issue 174492-4496 (September 2006): Epub 27 Jun. 2006. Scwarcznski, et al.,describe synthesization of a prodrug of paclitaxel which has a coumarinderivative conjugated to the amino acid moiety of isotaxel (O-acylisoform of paclitaxel). The prodrug was selectively converted toisotaxel by visible light irradiation (430 nm) with the cleavage ofcoumarin. Finally, paclitaxel was released by subsequent spontaneous O—Nintramolecular acyl migration.

In addition, the release element may include at least one of anadditional appropriate photodegradable/or biocompatible barrier formingmaterial.

In an embodiment, the release element 130 includes a release elementconfigured in a first medicament-release state and modifiable ex vivo toa second medicament-release state by an exposure to an energeticstimulus, also illustrated as stimulus 192. In an embodiment, anenergetic stimulus may include at least one of a mechanical stimulus, anon-ionizing radiation stimulus, an ionizing radiation stimulus, achemical stimulus, an acoustic stimulus, an ultrasound stimulus, a radiowave stimulus, a microwave stimulus, a light wave stimulus, or a thermalstimulus.

In an embodiment, the release element 130 is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to at least one of terahertzradiation, microwave radiation, and radio wave radiation, alsoillustrated as the stimulus 192. For example, radio wave radiation mayinclude, for example, at least one of ultra-high frequency radio waves(UHF), very high frequency radio waves (VHF), radio frequency (RF), orextremely low frequency (ELF) radio waves. In an embodiment, the releaseelement 130 includes at least one of a foil, gold foil, a liposome, wax,dielectric/wax composite. An example of a microwave responsive liposomeis described in U.S. Pat. No. 4,801,459 to R. Liburdy. An example of amicrowave responsive material, including a wax and a wax/dielectriccomposite, is described in United States Patent Application PublicationNo. 2005/0191708 to R. Saul, et al. In an embodiment, the releaseelement is configured in a first medicament-release state and modifiableex vivo to a second medicament-release state by an exposure to amagnetic stimulus. In an embodiment, the release element is configuredin a first medicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to an electric field stimulus.

In an embodiment, the release element is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to a chemical stimulus (notshown). For example, a chemical stimulus may include at least one of astimulus based on pH change, enzymatic exposure or catalysis. In anembodiment, a chemical stimulus may include a stimulus operable torelease or reverse a cooperative or a reversible molecular binding, or astimulus operable to form an irreversible binding.

In an embodiment, the release element 130 is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to a mechanical agitationstimulus (not shown). For example, a mechanical agitation stimulus mayinclude a shaking or spinning to rupture a membrane or a seal or a foil.In an embodiment, a release element is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an ex vivo exposure to a mechanical stimulus(not shown). For example, a mechanical stimulus may include shaking apiercing member against a foil release element. In an embodiment, therelease element is configured in a first medicament-release state andmodifiable ex vivo to a second medicament-release state by an ex vivoexposure to the stimulus, the release element including a mechanicallyactivatable structure (not shown). For example, the mechanicallyactivatable structure may include a foil or a pressure-rupturablemembrane, or a heat-activatable structure.

In an embodiment, the release element 130 is permeated, dissolved, ordisintegrated in response to the stimulus. In an embodiment, a releaseelement is changed such that it is permeated, dissolved, ordisintegrated in response to an in vivo environment of the animal 198where it would not have been so before exposure to the stimulus. In anembodiment, a release element is changed such that it forms a barrier,or is impermeable, solid, or integral in response to the exposure to thestimulus where it would not have been so before the exposure to thestimulus.

In an embodiment, the release element 130 is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to at least one of a thermal,acoustic stimulus and ultrasound. Examples of an acoustically activerelease element formed by conjugating liposomes and microbubbles aredescribed in A. Kheirolomoom, et al., Acoustically-active microbubblesconjugated to liposomes: Characterization of a proposed drug deliveryvehicle, 118 J CONTROL RELEASE, Issue 3, April 23; 118(3):275-284. Epub2006 Dec. 23.

In an embodiment, the release element 130 includes a release elementconfigured in a first medicament-release state and modifiable ex vivo toa second medicament-release state by an ex vivo exposure to at least oneof an activation stimulus, or an actuation stimulus. In an embodiment,the release element is configured in a first medicament-release stateand modifiable ex vivo to a second medicament-release state by anexposure to a de-activation stimulus.

In an embodiment, the release element 130 includes a release elementconfigured in a first medicament-release state and modifiable ex vivo toa second medicament-release state by an exposure to an ultrasoundstimulus. For example, the release element may include at least one ofliposomes, lipid microspheres, microbubbles, lipospheres, or liposomesresponsive to an ultrasound stimulus, which are described in U.S. Pat.No. 6,416,740 to Unger. In an embodiment, the release element includesat least one of polyanhidrides, polyglycolides, polyactides, poly(vinylacetate), poly(glycolic acid), poly(ethylene), poly(lactic acid), orchitosan. An example of ultrasound-responsive polymer is described in J.Kost, et al., Ultrasound-enhanced polymer degradation and release ofincorporated substances, 86 PROCEEDINGS OF THE NATIONAL ACADEMY OFSCIENCES OF THE USA, 7663-7666 (1989). In this article, Kost describesup to a 5-fold reversible increase in degradation rate and up to 20-foldreversible increase in release rate of incorporated molecules wereobserved with biodegradable polyanhydrides, polyglycolides, andpolylactides. This article also describes up to a 10-fold reversibleincrease in release rate of incorporated molecules within nonerodibleethylene/vinyl acetate copolymer were also observed. The release rateincreased in proportion to the intensity of ultrasound. Temperature andmixing were relatively unimportant in effecting enhanced polymerdegradation, whereas cavitation appeared to play a significant role.Another example of ultrasound-responsive polymer is described in J.Kost, et al., Ultrasonically controlled polymeric drug delivery,Makromolekulare Chemie 19 MACROMOLECULAR SYMPOSIA 275-285 (1988). Inthis article, Kost describes investigation of polymers that includelactic acid polymer, glycolic acid polymer, ethylene copolymer, vinylacetate copolymer. An example of ultrasound-responsive chitosan isdescribed in M. Tsaih, et al., Effect of the degree of deacetylation ofchitosan on the kinetics of ultrasonic degradation of chitosan; 90JOURNAL OF APPLIED POLYMER SCIENCE 3526-3531 (2003).

In an embodiment, the release element 130 includes at least one ofpolymeric micelle, liposome, lipid microsome, polymeric microsphere,nanoparticle, clathrate compound, cyclodextrin, gel, gel matrix,hydrogel, or cellulose. Examples of polymeric micelles are described inU.S. Pat. No. 7,229,973 to Bae, et al. Bae describes polymeric micellesincluding mixed micelles containing poly(L-histidine)-poly(ethyleneglycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol)block copolymer. Examples of polymer microspheres are described in U.S.Pat. No. 5,718,921 to Mathiowitz, et al. Mathiowitz describes polymermicrospheres built using polyanhydrides, polyorthoesters, polylacticacid polymers, and combinations thereof. Examples of cyclodextrin aredescribed in U.S. Pat. No. 7,270,808 to Cheng, et al., titled“Cyclodextrin-based polymers for therapeutics delivery.” Examples ofhydrogels are described in Lin et al., Hydrogels in controlled releaseformulations: Network design and mathematical modeling, ADVANCED DRUGDELIVERY REVIEWS 58 (2006) 1379-1408). Examples of cellulose aredescribed in U.S. Pat. No. 6,821,531 to Kumar.

In an embodiment, the release element 130 includes a release elementenclosing the chamber 120, configured in a first medicament-releasestate, and modifiable ex vivo to a second medicament-release state by anexposure to a stimulus, illustrated as the stimulus 192. For example,FIG. 1 illustrates an embodiment where the outer layer 110 has aspherical shape, the chamber may have similar nested spherical shape,and the release element having a spherical shape and surrounding thechamber. However, nothing in this document expresses or implies arequired similarity of shape among one or more of the chamber, therelease element, or the outer layer. For example, an embodiment mayinclude a liposome forming the release element and functionally defininga chamber.

In an embodiment, the release element 130 includes or defines a releaseelement encapsulating the chamber. In an embodiment, the release elementincludes a release element encapsulating the medicament 190 incooperation with the chamber wall 122, configured in a firstmedicament-release state, and modifiable ex vivo to a secondmedicament-release state by an exposure to the stimulus. For example,FIG. 2, infra, illustrates a release element 230 encapsulating themedicament 190 in cooperation with a chamber 220 as expressed or definedby a chamber wall 222. In an embodiment, the release element includes arelease element obstructing an aperture of the chamber. For example,FIG. 3, infra, illustrates a release element 330 in cooperation with achamber 320 as expressed by a chamber wall 322 obstructing an aperture332 of the chamber and preventing a discharge of the medicament 190along a fluid communication path 336 In an embodiment, the releaseelement includes at least two particles each collectively orrespectively forming a chamber carrying a respective instance of themedicament. For example, FIG. 4, infra, illustrates a release element430 that includes a particle 432 forming a chamber carrying an instanceof the medicament 190. An example of the particle 432 is additionallydescribed in conjunction with FIGS. 16, 20, and 23, and respectivecorresponding particle or polymeric material 1180, 1580, and 1680. Theparticle is configured in a first medicament-release state, andmodifiable ex vivo to a second medicament-release state by an exposureof the at least two particles to the stimulus. For example, the particlemay include a clathrate compound forming a host/guest relationship withmolecules of a medicament. For example, the particle may include atleast one of hydrogels, liposomes, or dendrimers configured to carry themedicament in an association with their pores, interstitial cavities,structural interstices, bonds, or amorphous cavities.

In an embodiment, the release element includes a labile bond between amolecule of the medicament and a bioactivity inhibiting moleculeconfigured in a first medicament-release state and modifiable ex vivo toa second medicament-release state by an exposure of the labile bond tothe stimulus (not shown).

Referring again to FIG. 1, in an embodiment, the release element 130 isconfigured in a first medicament-release state and modifiable ex vivo toa second medicament-release state by an exposure to the stimulus, andconfigured to contain the medicament 190 at least until the final dosageform 102 is administered into the animal 198.

FIG. 1 illustrates an embodiment having the chamber 120 formed withinthe outer layer 110 and configured to carry the medicament 190. In anembodiment, the chamber 120 is substantially defined within the outerlayer and configured to carry the medicament until released by therelease element. For example, FIG. 2 illustrates an embodiment thatincludes the chamber 220 substantially defined within the outer layer210 and configured to carry the medicament 190 until released by therelease element 230. FIG. 3 illustrates an embodiment that includes thechamber 320 substantially defined within the outer layer 310 andconfigured to carry the medicament 190 until released by the releaseelement 330.

In an embodiment (not shown), the release element and chamber both maybe formed by a particle, such as a liposome, or a hydrogel. In suchembodiment, the chamber includes at least one chamber substantiallywithin the outer layer of the particle and configured to carry themedicament.

In an embodiment, the chamber 120 includes a chamber configured toconfine the medicament 190 in cooperation with the release element 130.In an embodiment (not shown), the chamber includes at least one chamberconfigured to confine the medicament in a structural cooperation withthe release element. In an embodiment (not shown), the chamber isconfigured to initially carry the medicament. The chamber is alsoconfigured to release at least a portion of the medicament upon at leastone of a reconfiguration, bursting, puncture, permeation, dissolution,and disintegration of the release element 130.

In an embodiment (not shown), the chamber 120 includes a first chamberconfigured to carry a first medicament and a second chamber configuredto carry a second medicament. An example of the first chamber configuredto carry a first medicament and the second chamber configured to carry asecond medicament is described in conjunction with FIG. 5 and chamber520A and chamber 520B. In an embodiment (not shown), the chamberincludes a first chamber configured to carry a first constituent of themedicament and a second chamber configured to carry a second constituentof the medicament. In an embodiment (not shown), the chamber includes afirst chamber configured to carry a first reactant of the medicament anda second chamber configured to carry a second reactant of themedicament. In an embodiment (not shown), a combination of the firstreactant and the second reactant in response to an ex vivo exposure ofthe release element initiates a chemical activation or a synthesis ofthe medicament and a physical releasability of the medicament. In anembodiment (not shown), a combination of the first reactant and thesecond reactant in response to an ex vivo exposure of the releaseelement initiates a chemical activation or a synthesis of the medicamentbut does not provide a physical releasability of the medicament. In anembodiment, the resulting medicament product can be released in vivothrough the release characteristics of the outer layer. Alternatively,the physical releasability of the medicament may occur by another exvivo exposure of the dosage form to a stimulus, such as the stimulus192.

In an embodiment shown in FIG. 1, the final dosage form 102 includes acontainment element 140 retaining the medicament 190 within the finaldosage form until the dosage form is administered to the animal 198. Thecontainment element can be used in situations where the medicament is aliquid or other material that is prone to seepage or discharge throughthe outer layer. In embodiment, the containment element may include aseparate structure, such as a film or coating, retaining the medicament.Such a containment element 140 may form an exterior layer over the outerlayer 110, or may form a layer interposed between the outer layer 110and the chamber 120. In an embodiment, the containment element 140 mayinhibit a discharge of the medicament 190 from the final dosage form 102prior to its introduction into the animal 198, without regard to whetherthe release element is in its first medicament-release state or itssecond medicament-release state. In an embodiment, the containmentelement 140 includes a containment element 140 retaining the medicament190 within the final dosage form 102 until the final dosage form 102 isexposed to an in vivo environment in the animal 198, and to modulate arelease of at least a portion of the medicament 190 in vivo uponadministration of the final dosage form 102 to the animal 198. In anembodiment, the containment element may be formed by a combination ofthe outer layer 110 and the release element 130.

In an embodiment, the containment element 140 includes a containmentlayer configured to encompass the medicament 190 within the final dosageform 102 until the final dosage form is administered to the animal 198.For example, the containment element 140 may include a coating coveringthe outer layer 110 of the final dosage form 102, such as an entericcoating configured to prevent a release of the medicament from the finaldosage form until the final dosage form is administered to the animal.In another example, the containment element 140 may include a coatingcovering the release element 130 of the final dosage form 102. In anembodiment, the containment element includes a containment enveloperetaining the medicament within the final dosage form until the dosageform is administered to the animal.

In an embodiment, the containment element 140 includes an entericcoating. The enteric coating may include gelatin or celluloseencapsulation. In an embodiment, the containment element includes ahydroxypropyl methylcellulose acetate succinate (HPMCAS) based coatingor a methacrylic acid copolymer based coating, for example such asdescribed in U.S. Pat. No. 7,138,143 to Mukai, et al. In an embodiment,the containment element includes a polymer coating, such as an acidicgroup-containing (meth)acrylate copolymer, shellac, HPMCP(hydroxypropylmethylcellulose phthalate), CAP (cellulose acetatephthalate), HIPMC-AS (hydroxypropylmethylcellulose acetate succinate) orpolyvinyl acetate phthalate, for example such as described in U.S. Pat.No. 6,887,492 to Kay, et al. In an embodiment, the containment elementincludes a polymer coating of a (meth)acrylate copolymer comprisingfree-radical polymerized C.sub.1- to C.sub.4-alkyl esters of acrylic ormethacrylic acid and (meth)acrylate monomers with a quaternary anunoniumgroup in the alkyl radical, a (meth)acrylate copolymer of 20 to 40% byweight of polymerized ethyl acrylate and 60 to 80% by weight ofpolymerized methyl methacrylate, ethylcellulose or polyvinyl acetate.For example, as described in U.S. Pat. No. 6,897,205 to Beckert et al.In an embodiment, the containment element includes a cellulose acetatephthalate polymer coating material, for example, as described in U.S.Pat. No. 5,686,106 to Kelm, et al. In an embodiment, the containmentelement includes a cellulose acetate phthalate; cellulose acetatetrimellitate; hydroxypropyl methylcellulose phthalate; hydroxypropylmethylcellulose acetate succinate; polyvinyl acetate phthalate;poly(methacrylic acid, methyl methacrylate) 1:1; or poly(methacrylicacid, ethyl acrylate) 1:1; and compatible mixtures thereof. In anotherembodiment, the containment element includes a poly(methacrylic acid,methyl methacrylate) 1:2, or a mixture of poly(methacrylic acid, methylmethacrylate) 1:1 and poly(methacrylic acid, methyl methacrylate) 1:2 ina ratio of about 1:10 to about 1:2. For example, as described in U.S.Pat. No. 5,686,105 to Kelm, et al.

In an embodiment illustrated in FIG. 2 infra, the containment element240 includes a containment element 240 configured to prevent a releaseof the medicament 190 from the final dosage form 202 until the finaldosage form 202 is introduced into the animal 198.

Returning to FIG. 1, in an embodiment, the medicament 190 includes atleast one of an agent, treatment agent, drug, prodrug, therapeutic,nutraceutical, medication, vitamin, nutritional supplement, medicine,remedy, medicinal substance, or cosmetic. In an embodiment, themedicament includes a first reactant of the medicament and a secondreactant of the medicament. In an embodiment, the medicament includes atleast one prodrug and optionally an activating-enzyme of the prodrug. Inan embodiment, the chamber includes a first chamber configured to carrya prodrug, and a second chamber configured to carry an activating enzymeof the prodrug.

In an embodiment, the final dosage form 102 may further include aindicator element 180 configured to indicate an exposure of the releaseelement 130 to the stimulus 192. In an embodiment, the indicator element180 includes an indicator element 180 configured to optically indicatean exposure of the release element to the stimulus 192 by at least oneof dielectric, a conductivity, or ultrasonic profile responsive to anexposure of the release element to the stimulus. The indicator element180 including, for example, at least one of 4-keto-bacteriorhodopsinfilms, cinnamylidene acetyl chloride, α-methylcinnamylidene acetylchloride, α,γ-dimethylcinnamylidene acetyl chloride,α-phenylcinnamylidene acetyl chloride, α-phenoxycinnamylidene acetylchloride, and cyanocinnamylidene acetyl chloride, leuco dye-serumalbumin albumin complexes, azo dyes, or poly(ethylene glycol). Examplesof bacteriorhodopsin films are described in A. Druzhko, et al.,4-Keto-bacteriorhodopsin films as a promising photochromic andelectrochromic biological material, BIOSYSTEMS. 1995; 35(2-3): 129-32.Examples of hydrophilic photosensitive polymers are described in U.S.Pat. No. 5,990,193 to Russell, et al. Examples of photosensitivecompositions for detection of radiation in the ultraviolet wavelength,including leuco dye-serum albumin complexes, are described in U.S. Pat.No. 4,466,941 to Cerami, et al. Examples of using azo dye for anindicator is described in U.S. Pat. No. 5,679,442. Examples ofpoly(ethylene glycol) are described in U.S. Pat. No. 5,990,193 toRussell, et al., and in Zhong, et al., Photodegradation Behavior ofPolycaprolactone-Poly(ethylene glycol) Block Copolymer, Vol. 10, No. 4CHINESE CHEMICAL LETTERS 327-330 (1999).

In an embodiment depicted in FIG. 1, the indicator element 180 includesan electronically-detectable indicator element 180 configured toindicate an exposure of the release element 130 to the stimulus 192. Forexample, the electronically-detectable indicator element 180 may includea substance, material, or device having a conductive property that makesan electronically-detectable change in response to an exposure to thestimulus 192. An example of such substance, material, or device includesa shape memory alloy switch that responds to heat described in U.S. Pat.No. 5,410,290 to Cho. Other examples of such substances, materials, ordevices include a material that polymerizes in the presence of anultrasound and changes a conductive property in response, such as theultrasonic polymerization of methyl methacrylate described in U.S. Pat.No. 5,466,722 to Stoffer, et al., the heat or UV radiation triggeredpolymerization of acrylamide, or the microwave triggered polymerizationof trimethylene carbonate. Another example of such substances,materials, or devices include the use of bistable compounds whoseconductivity changes based upon exposure to electromagnetic radiation asdescribed in U.S. Pat. No. 7,175,961 to Beck, et al. Another exampleincludes a metal film or foil degradable by microwaves to release themedication whose state can degradation detected electrically.

In an embodiment, the indicator element 180 includes anelectronically-detectable indicator element 180 configured to indicatean exposure of the release element 130 to the stimulus 192. For example,the electronically-detectable indicator element 180 may include adielectric element having a property that makes anelectronically-detectable change in response to an exposure to thestimulus 192. An example of such a dielectric element may include aone-time programmable memory cell described in U.S. Pat. No. 7,256,446,to Hu, et al., or a switch comprising microelectromechanical elementsdescribed in U.S. Pat. No. 7,336,474 to Lerche, et al.

In an example, the electronically-detectable indicator element 180 mayinclude an element having a permittivity that makes anelectronically-detectable change in response to an exposure of therelease element to the stimulus 192. An example of such an elementhaving a permittivity may include photonic crystals whose permittivitychanges through the addition of photonic and/or electrical energy asdescribed in U.S. Pat. No. 6,859,304 to Miller, et al.

In another example, the electronically-detectable indicator element 180may include an element having an ultrasonic profile that makes anultrasound-discernable change in response to an exposure of the releaseelement to the stimulus 192. An example of an element having anultrasonic profile that includes a polymer monitorable using thecontinuous wave ultrasonic process monitor is described in U.S. Pat. No.7,017,412 to Thomas, et al. Another example of an element having anultrasonic profile that includes a polymer monitorable using theapparatus for degree on doneness is described in U.S. Pat. No. 7,191,698to Bond, et al. A further example of an element having an ultrasonicprofile that includes a degradable metal film or metal foil.

In another example, the electronically-detectable indicator element 180may include a carrier, admixture, diluent, or excipient having aproperty that makes an ultrasound-discernable change in response to anexposure of the release element to the stimulus 192. For example, anadmixture may include a phase change material (PCM) as an inert fillerand having a property that makes an ultrasound-discernable change inresponse to an exposure of the release element to ultrasound. Examplesof such PCMs include polyvinyl alcohol (PVA)-stearic acid (SA) andpolyvinyl chloride (PVC)-stearic acid (SA). An example ofPolymer-stearic acid blend is described in Ahmet Sari, et al.,Polymer-stearic acid blends as form-stable phase change material forthermal energy storage, 64 JOURNAL OF SCIENTIFIC & INDUSTRIAL RESEARCH,at pp. 991-996 (December 2005). Other examples are described in UnitedStates patent application No. 2007/0249753 to Lin, et al. (polyetherfatty-acid ester (polyethylene glycol or polytetramethylene glycol basepolymer), and U.S. Pat. No. 5,565,132 to Salyer (Addition of microwaveabsorber to make PCM materials sensitive to microwaves). Ultrasonicdetection or discernment of phase changes in a PCM may be implementedusing techniques described by A. W. Aziz, & S. N. Lawandy, Ultrasonicdetection of segmental relaxations in thermoplastic polyurethanes, 31JOURNAL OF APPLIED POLYMER SCIENCE 1585 (Issue 6, 2003) or S. L. Morton,Ultrasonic cure monitoring of photoresist during pre-exposure bakeprocess, ULTRASONICS SYMPOSIUM, 1997. PROCEEDINGS. 1997 IEEE Volume 1,at 837-840 (October 1997).

The indicator element 180 (as enumerated in FIG. 1) can be madebiocompatible so as to not cause an adverse reaction in the animal.Biocompatibility can be achieved through the use of a biocompatiblematerial or through the use of a minimal amount of material so that anyadverse reaction to the indicator element 180 is minimized.

FIG. 2 illustrates an environment 200 that includes the animal 198, across-sectional view of an example final dosage form 202 foradministering the medicament 190 to the animal, and the examplestimulation source 194 operable to emit the stimulus 192. In anembodiment, the final dosage form includes a dosage form havingcompleted a manufacturing or production process. In an embodiment, thefinal dosage form includes a product, finished tablet, or capsule readyfor distribution to a hospital, pharmacy, or retail store forindividualizing to a particular animal, such as the animal 198. In anembodiment, the final dosage form may include a tablet shape, aspherical shape, or an ellipsoidal shape. In an embodiment, the finaldosage form may include a structure or a particle carryable ortransportable by a liquid or other fluid carrier.

The final dosage form 202 includes an outer layer 210, the releaseelement 230, and the chamber 220 as expressed or defined by the chamberwall 222. The release element is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to a stimulus. For example, thestimulus may include the stimulus 192. The chamber includes a chamberwall 222, is substantially within the outer layer, and is configured tocarry the medicament 190. In an embodiment, the final dosage form mayinclude an indicator element 280. In an embodiment, the final dosageform may include a containment element 240.

The environment 200 illustrates an embodiment where the release element230 encompasses the medicament 190 in cooperation with the chamber 220as expressed or defined by the chamber wall 222. The outer layer 210 andthe release element 230 are cooperatively retaining the medicament 190if the release-element is in a first medicament-release state and allowan in vivo discharge of at least a portion of the medicament from thechamber if the release-element is in a second medicament release state.In an embodiment, the release element may include at least one of apoly(vinyl alcohol), gel, gel matrix, hydrogel, and azopolymer photo orlight modifiable substance as described above. In an embodiment, therelease element may include at least one of a polyanhidride,polyglycolide, polyactide, poly(vinyl acetate), poly(glycolic acid),poly(ethylene), poly(lactic acid), chitosan, or an acoustic orultrasound-modifiable substance as described above. For example, whenthe first medicament-release state is configured to retard medicamentrelease and the second medicament-release state is configured to allowmedicament release in vivo, the release element when configured in thefirst medicament-release state will retard medicament release from thefinal dosage form upon administration of the final dosage form into theanimal. For example, in a first medicament release state, the releaseelement is impermeable to the environment outside the final dosage form,and impermeable to the medicament in the chamber. Following exposure toan appropriately configured stimulus, the release element achieves asecond medicament release state that is, for example, permeable to themedicament. The second medicament release state may include, forexample, a state where the release element changes shape or size (e.g.,expands, shrinks), dissolves, or dissipates upon exposure to an aqueousenvironment, gastric juices or a certain pH environment.

FIG. 3 illustrates a non-limiting environment 300 that includes theanimal 198, a cross-sectional view of an example final dosage form 302for administering the medicament 190 to the animal, and the examplestimulation source 194 operable to emit the stimulus 192. In anembodiment, the final dosage form includes a dosage form havingcompleted a manufacturing or production process. In an embodiment, thefinal dosage form includes a product, finished tablet, or capsule readyfor distribution to a hospital, pharmacy, or retail store forindividualizing to a particular animal, such as the animal 198. In anembodiment, the final dosage form may include a tablet shape, aspherical shape, or an ellipsoidal shape. In an embodiment, the finaldosage form may include a structure or a particle carryable ortransportable by a liquid or other fluid carrier.

The final dosage form 302 includes an outer layer 310, a chamber 320,and a release element 330. The final dosage form also includes a releasepassageway 332 configured to provide a medicament communication pathwaybetween the chamber and the environment through an aperture 334 in theouter layer. The release element is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to a stimulus. For example, thestimulus may include the stimulus 192. The chamber includes a chamberwall 322, is substantially within the outer layer, and is configured tocarry the medicament 190. In an embodiment, the final dosage form mayinclude an indicator element 380. In an embodiment, the final dosageform may include a containment element 340.

FIG. 3 illustrates a non-limiting embodiment wherein an embodiment ofthe final dosage form 302 includes the release element 330 retaining themedicament 190 in cooperation with the chamber 320 as expressed by thechamber wall 322. The outer layer 310 and the release-element 330 arecooperatively retaining the medicament 190 if the release-element is inone medicament-release state and allowing an in vivo discharge of atleast a portion of the medicament from the chamber if therelease-element is in another medicament release state. When therelease-element is in a state that releases the medicament, themedicament may discharge or flow along the fluid communication path 336expressed or defined at least in part by the release passageway 332.

In an embodiment, the release element may include at least one of apoly(vinyl alcohol), gel, gel matrix, hydrogel, and azopolymer photo orlight modifiable substance as described above. In an embodiment, therelease element may include at least one of a foil, gold foil, wax, ordielectric/wax composite microwave modifiable substance. In anembodiment of this example, the release element may include at least oneof a polyanhidride, polyglycolide, polyactide, poly(vinyl acetate),poly(glycolic acid), poly(ethylene), poly(lactic acid), chitosan, or anacoustic or ultrasound-modifiable substance as described above. Forexample, when the first medicament-release state is configured to retardmedicament release and the second medicament-release state is configuredto allow medicament release in vivo, the release element when configuredin the first medicament-release state will retard medicament releasefrom the release passageway 332 and the aperture 334 of the final dosageform upon administration of the final dosage form into the animal.

FIG. 4 illustrates an environment 400 that includes the animal 198, across-sectional view of an example final dosage form 402 foradministering the medicament 190 to the animal, and the examplestimulation source 194 operable to emit the stimulus 192. In anembodiment, the final dosage form 402 includes a dosage form havingcompleted a manufacturing or production process. In an embodiment, thefinal dosage form 402 includes a product, finished tablet, or capsuleready for distribution to a hospital, pharmacy, or retail store forindividualizing to a particular animal, such as the animal 198. In anembodiment, the final dosage form 402 may include a tablet shape, aspherical shape, or an ellipsoidal shape. In an embodiment, the finaldosage form 402 may include a structure or a particle carryable ortransportable by a liquid or other fluid carrier.

The final dosage form 402 includes an outer layer 410, a chamber 420,and a release element 430. The release element is configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure to a stimulus. For example, thestimulus may include the stimulus 192. The chamber includes a chamberwall 422, is substantially within the outer layer, and is configured tocarry the medicament 190. In an embodiment, the final dosage form 402may include an indicator element 480. In an embodiment, the final dosageform 402 may include a containment element 440.

In an embodiment, the chamber 420 includes a chamber substantiallywithin the outer layer 410 and configured to carry the medicament 190.In an embodiment, the chamber encloses at least two structures withinthe chamber having respective subchambers configured to carry themedicament. For example, such at least two structures may include atleast two pores, molecular structures having interstitial cavities,smaller chambers, molecular structure having interstices, or molecularstructure having amorphous cavities. In an embodiment, the chamber maycontain at least one of an absorbent, liposome, or hydrogel molecularstructure which define respective chambers therein. For example, atleast two particles may be located in a cavity, such as the chamber 120,and in themselves define a distributed chamber by an aggregation oftheir pores, interstitial cavities, smaller chambers, interstices of amolecular structure, or amorphous cavities. In another example, at leasttwo microparticles may be throughout a carrier having an outer layer,each microparticle having an effective chamber. In an embodiment, thechamber is located substantially within the release element 430. In anembodiment, the distributed chamber is located substantially within theouter layer 410.

The final dosage form 402 may include a release element 430 that isassociated with the medicament 190 in the chamber 420. In an embodiment,the release element 430 may include a carrier, admixture, diluent, orexcipient configured in a first medicament-release state and modifiableex vivo to a second medicament-release state by an ex vivo exposure tothe stimulus 192. Particles of such a carrier, admixture, diluent, orexcipient may be configured to retain or bind to particles of themedicament 190 and reduce its bioavailability if the release-element 430is in a first medicament-release state, and release from or unbindparticles of the medicament 190 and allow an in vivo discharge of atleast a portion of the medicament 190 from the chamber 420 if therelease-element 430 is in a second medicament release state.

In an embodiment, an instance of the final dosage form 402 may carry atleast two particles, small particles, or microparticles that eachinclude a portion that forms a release element 430 modifiable ex vivo byexposure to the stimulus 192, and a chamber (not shown). The chambers ofthe at least two particles, small particles, or microparticles eachconfigured to carry a respective instance of the medicament, andcollectively forming a distributed chamber. For example, the at leasttwo particles, small particles, or microparticles may include hydrogels,liposomes, or dendrimers having pores, interstitial cavities, structuralinterstices, bonds, or amorphous cavities configurable to carrymolecules of the medicament. The at least two particles, smallparticles, or microparticles are configured in a firstmedicament-release state and modifiable ex vivo to a secondmedicament-release state by an exposure of the at least two particles,small particles, or microparticles to the stimulus. For example,photosensitive hydrogel particles may carry the medicament. In anembodiment, microwave sensitive liposomes may carry the medicament. Inan embodiment, the release element includes a labile bond between amolecule of the medicament and molecule of a bioactivity inhibitingmolecule configured in a first medicament-release state and modifiableex vivo to a second medicament-release state by an exposure of thelabile bond to the stimulus (not illustrated).

FIG. 5 illustrates an environment 500 that includes the animal 198, across-sectional view of a final dosage form 502 for transporting amedicament to the animal. The medicament is illustrated as a firstmedicament 190A and second medicament 190B. In an embodiment, the finaldosage form includes a dosage form having completed a manufacturing orproduction process. In an embodiment, the final dosage form 502 includesa product, finished tablet, or capsule ready for distribution to ahospital, pharmacy, or retail store for individualizing to a particularanimal, such as the animal 198. In an embodiment, the final dosage form502 may include a tablet shape, a spherical shape, or an ellipsoidalshape. In an embodiment, the final dosage form 502 may include astructure or a particle carryable or transportable by a liquid or otherfluid carrier.

The final dosage form 502 includes an outer layer 510, and at least twodosage elements. The at least two dosage elements are illustrated as APortion and B Portion, and by “A” and “B” after certain referencenumbers in FIG. 5. The A Portion includes a chamber 520A, a releaseelement 530A, and a medicament 190A. In an embodiment, the A Portionincludes a containment element 540A. In an embodiment, the A Portionincludes an indicator element 580A. The B Portion includes a chamber520B, a release element 530B, and a medicament 190B. In an embodiment,the B Portion includes a containment element 540B. In an embodiment, theB Portion includes an indicator element 580B.

In an embodiment, the A Portion of the final dosage form 502 may besubstantially similar to the chamber 120, the release element 130, thecontainment element 140, and the indicator element 180 of FIG. 1. In anembodiment, the A Portion may be substantially similar to the chamber220, the release element 230, the containment element 240, and theindicator element 280 of FIG. 2. In an embodiment, the A Portion may besubstantially similar to the chamber 320, the release element 330, thecontainment element 340, and the indicator element 380 of FIG. 3. In anembodiment, the A Portion may be substantially similar to the chamber420, the release element 430, the containment element 440, and theindicator element 480 of FIG. 4. Similarly, the B Portion of the finaldosage form 502 may be substantially similar to that described inconjunction with at least one of FIG. 1, FIG. 2, FIG. 3, or FIG. 4.

In an embodiment, the first medicament 190A and the second medicament190B may be substantially similar instances of the same medicament. Inan embodiment, the first medicament 190A and the second medicament 190Bmay be substantially similar instances of the same medicament, but insubstantially differing dosage amounts. For example, the firstmedicament 190A may be, for example, a 50-milligram dose of a medicamentand the second medicament 190B may be, for example, a 100-milligram doseof the same medicament. In an embodiment, the first medicament 190A andthe second medicament 190B may be substantially similar instances of thesame medicament, but in substantially differing dosage characteristics,such as a regular release formulation and a sustained releaseformulation. In an embodiment, the first medicament 190A and the secondmedicament 190B may be different medicaments.

In use, the A Portion and the B Portion of the final dosage form 502 maybe individually or collectively exposed ex vivo to a stimulus,illustrated as the stimulus 192. For example, the final dosage form 502can be configured to provide any of three possible dosage levels of themedicament. For example, where the first medicament 190A is a50-milligram dose of a medicament and the second medicament 190B is a100-milligram dose of a same medicament, where the release element 530Aand release element 530B are modifiable ex vivo by the same stimulus,such as microwave energy, and where the first medicament-release stateis configured to retard medicament release in vivo and the secondmedicament-release state is configured to allow medicament release invivo, irradiation of the A Portion with microwave energy will actuatethe A Portion and make 50-milligrams of the medicament available uponadministration of the final dosage form to the animal 198. Similarly,irradiation of the B Portion with microwave energy will actuate the BPortion and make 100-milligrams of the medicament available uponadministration of the final dosage form to the animal. Further,irradiation of both the A Portion and the B Portion with microwaveenergy will actuate both Portions and make 150-milligrams of themedicament available upon administration of the final dosage form to theanimal. In another example, the first medicament 190A is a 100-milligramdose of a first medicament and the second medicament 190B is a100-milligram dose of a second medicament. Selective irradiation of theA Portion or the B Portion will make one or both of the medicamentsbioavailable upon administration of the final dosage form to the animal.In a further example, the release element 530A is modifiable ex vivo bya first stimulus and the release element 530B is modifiable ex vivo bythe second and different stimulus.

FIG. 6 illustrates an example environment 600 that includes an articleof manufacture 601. The article of manufacture includes a package 660containing a final dosage form 602 and providing an instruction 670. Thefinal dosage form includes a medicament 190, an outer layer 610, arelease element 630, and a chamber 620. The release element isconfigured in a first medicament-release state and modifiable ex vivo toa second medicament-release state by an exposure to anactuation-stimulus. The chamber lies substantially within the outerlayer and is configured to carry the medicament. The instructionincludes instruction for preparation of the final dosage form for anefficacious administration to an animal by an exposure of the releaseelement of the final dosage form to the stimulus.

In an embodiment, the final dosage form 602 may be substantially similarto the final dosage form 102 of FIG. 1. In an embodiment, the finaldosage form 602 may be substantially similar to the final dosage form202 of FIG. 2. In an embodiment, the final dosage form 602 may besubstantially similar to the final dosage form 302 of FIG. 3. In anembodiment, the final dosage form 602 may be substantially similar tothe final dosage form 402 of FIG. 4. In an embodiment, the final dosageform 602 may be substantially similar to the final dosage form 502 ofFIG. 5.

In an embodiment, the instruction 670 includes at least one ofinformation indicating an actuation-stimulus type, an actuation-stimuluswavelength, an actuation-stimulus intensity, an actuation-stimulusduration, a spatial distribution of the stimulus relative to the finaldosage form, a target-value for an exposure indicator, or a combinationthereof. For example, the information indicating a spatial distributionof the stimulus relative to the final dosage form may includeinformation corresponding to aiming the stimulus, such as toward a righthand portion, a center portion, or a left hand portion of the finaldosage form. In an embodiment, the instruction includes an instructionpresented by at least one of a label (not shown) on the package 660, aninsert in the package, illustrated as the instruction 670, or an addressto electronically published content (not shown). In an embodiment, theinstruction includes instruction for preparation of the final dosageform for an efficacious administration to an animal by a human-initiatedexposure of the release element of the final dosage form to theactuation-stimulus.

In an embodiment, the final dosage form 602 further includes acontainment element 640 retaining the medicament within the final dosageform until the final dosage form is introduced into the animal. In anembodiment, the final dosage form includes an indicator element 680configured to indicate an exposure of the release element to thestimulus. In an embodiment, the instruction 670 includes informationindicating an expected value of the indicator element.

FIG. 7 illustrates an example operational flow 700 modulating amedicament-release characteristic of a final dosage form. A startoperation occurs in an environment 705 that includes the final dosageform. The final dosage form includes a medicament, an outer layer, arelease element configured in a first medicament-release state andmodifiable ex vivo to a second medicament-release state by an exposureto the stimulus, and a chamber substantially within the outer layer andconfigured to carry the medicament. After the start operation, theoperational flow includes an individualization operation 710. Theindividualization operation includes irradiating the release element ofthe final dosage form ex vivo with a non ionizing radiation, thenon-ionizing radiation selected to transform the release element fromthe first medicament-release state to the second medicament-releasestate. For example, the irradiating the release element of the finaldosage form ex vivo with the stimulus may occur in a hospital pharmacy,a retail pharmacy, a battlefield hospital, a veterinary facility, orother location dispensing medicaments. In another example, theirradiating a release element of the final dosage form ex vivo with thestimulus may occur in a persons home. The operational flow then proceedsto an end operation. In an alternative embodiment, the final dosage formfurther includes a containment element retaining the medicament withinthe final dosage form before introduction of the final dosage form intothe animal.

FIG. 8 illustrates an alternative embodiment of the operational flow 700of FIG. 7. The individualization operation 710 may include at least oneadditional operation. The at least one additional operation may includeat least one of an operation 712, an operation 714, an operation 716, anoperation 718, or an operation 722. The operation 712 includesirradiating in response to a human-initiated activation a releaseelement of the final dosage form ex vivo with a non-ionizing radiation.The operation 714 includes automatically initiating an ex vivoirradiation with a non-ionizing radiation a release element of the finaldosage. The operation 716 includes irradiating a first release elementof the final dosage form ex vivo with a non-ionizing radiation withoutirradiating a second release element of the final dosage form with thestimulus. The operation 718 includes irradiating a first release elementof the final dosage form ex vivo with a non-ionizing radiation withoutirradiating a second release element of the final dosage form with thenon-ionizing radiation. The first release element is associated with afirst chamber carrying a first instance of the medicament, and thesecond release element is associated with a second chamber carrying asecond instance of the medicament. The operation 722 includesirradiating a first release element of the final dosage form ex vivowith a non-ionizing radiation without irradiating a second releaseelement of the final dosage form with the stimulus. The first releaseelement is associated with a first chamber carrying a first medicament,and the second release element is associated with a second chambercarrying a second medicament.

FIG. 9 illustrates an example operational flow 800 fulfilling a requestspecifying a dose of a medicament for an individual animal. A startoperation occurs in an environment that includes a final dosage form.The final dosage form includes an outer layer, a release elementconfigured in a first medicament-release state and changeable to asecond medicament-release state by an exposure to the stimulus, achamber substantially within the outer layer and configured to carry themedicament, and the medicament. In an alternative embodiment, the finaldosage form further includes a containment element retaining themedicament within the final dosage form before introduction of the finaldosage form into the animal. After the start operation, the operationalflow includes a picking operation 810. The picking operation includeschoosing pursuant to the request an instance of a final dosage form thatincludes the medicament. A decision operation 830 includes selecting astimulus configured to change or transform a medicament-release state ofa release element of the final dosage form. A customization operation850 includes initiating an exposure of the release element of the choseninstance of the final dosage form to the selected stimulus. Theoperational flow then proceeds to an end operation.

In use of an embodiment, a person such as a pharmacist working in apharmacy may receive a prescription specifying a dose of a medicamentfor a patient. A pharmacy typically may have available several differentfinal dosage forms capable of administering the prescribed medicamentdose. For example, the available different dosage forms may include atleast one of the embodiments of final dosage forms illustrated in FIGS.1-5. In a picking operation, the pharmacist chooses pursuant to therequest an instance of a final dosage form that includes the medicament.In a decision operation, the pharmacist selects a stimulus effective tochange a medicament-release state of a release element of the finaldosage form. The pharmacist may select the stimulus after consultingwith an instruction presented by at least one of a label on boxcontaining the chosen instance of a final dosage form, a package insertin the box, or an address to electronically published content indicatedon the label, or package insert. The pharmacist enters the selectedstimulus setting for a stimulus emitter, such as the stimulus source 194of FIG. 1. In a customization operation, the pharmacist initiates anexposure of the release element of the chosen instance of the finaldosage form to the selected stimulus. The pharmacist may confirmexposure of the release element to the stimulus by referring to theindicator element. For example, the indicator element may change colorin response to an exposure to the selected stimulus. If the prescriptionspecifies multiple doses of the medicament for the patient, thepharmacist may repeat the above sequence until sufficient doses havecustomized. Alternatively, and if appropriate for the chosen finaldosage forms, multiple instances of the final dosage form may be ex vivoexposed to the selected stimulus at one time.

FIG. 10 illustrates an alternative embodiment of the example operationalflow 800 of FIG. 9. The picking operation 810 may include at least oneadditional operation. The at least one additional operation may includean operation 812, or an operation 814. The operation 812 includeschoosing pursuant to at least one of an order or a prescription aninstance of a final dosage form that includes the medicament. Theoperation 814 includes at least one of physically or manually choosingpursuant to the request an instance of a final dosage form that includesthe medicament.

FIG. 11 illustrates another embodiment of the example operational flow800 of FIG. 9. The decision operation 830 may include at least oneadditional operation. The at least one additional operation may includean operation 832, an operation 834, or an operation 836. The operation832 includes selecting a stimulus having an attribute indicated by atleast one of a manufacturer of the final dosage form, an instructionpackaged with the dosage form, an electronically published content, anda printed publication as effective to change a medicament-release stateof a release element of the final dosage form. For example,electronically published content may include a website maintained by themanufacturer of the final dosage form. In a further example, a printedpublication may include a reference book, such as Physician's DeskReference. The operation 834 includes selecting a stimulus configured byat least one of a type, amount, level, wavelength, spectrum, waveform,spatial distribution, duration, or pulse attribute to change amedicament-release state of a release element of the final dosage form.The operation 836 includes selecting a stimulus configured to change amedicament-release state of a release element of the final dosage formand to make the request-specified dose of medicament dose bioavailableby the final dosage form.

FIG. 12 illustrates an embodiment of the example operation 800 of FIG.9. The customization operation 850 may include at least one additionaloperation. The at least one additional operation may include anoperation 852, an operation 854, or an operation 856. The operation 852includes changing a medicament-release state of the release element ofthe chosen instance of the final dosage form by initiating an exposureof the release element of the chosen instance of the final dosage formto the selected stimulus. The operation 854 includes preparing abioavailable dose of the medicament of the final dosage form infulfillment of the request by initiating an exposure of the releaseelement of the chosen instance of the final dosage form to the selectedstimulus. The operation 856 includes initiating an exposure of therelease element of the chosen instance of the final dosage form to theselected stimulus in fulfillment of the request.

FIG. 13 illustrates an embodiment of the example operational flow 800 ofFIG. 9. The operation 870 may include at least one additional operation.The at least one additional operation may include an operation 872, anoperation 874, or an operation 876. The operation 870 may include atleast one additional operation. The at least one additional operationmay include an operation 872, an operation 874, or an operation 876. Theoperation 872 includes optically verifying the exposure of the releaseelement of the chosen instance of the final dosage form to the selectedstimulus. For example, optically verifying the exposure may beimplemented using human vision, machine vision, or ultrasoundtechniques. The operation 874 includes electronically verifying theexposure of the release element of the chosen instance of the finaldosage form to the selected stimulus. For example, electronicallyverifying the exposure of the release element may be implemented using adielectric element having a property that makes an electronicallydiscernable change in response to an exposure to the stimulus. Theoperation 876 includes quantifying the exposure of the release elementof the chosen instance of the final dosage form to the selectedstimulus. The operation 876 may include at least one additionaloperation. The at least one additional operation may include anoperation 878, or an operation 882. The operation 878 includesinitiating another exposure of the release element of the choseninstance of the final dosage form to the selected stimulus in responseto the quantifying the exposure of the release element of the choseninstance of the final dosage form to the selected stimulus. Theoperation 882 includes terminating the exposure of the release elementof the chosen instance of the final dosage form to the selected stimulusin response to the quantifying the exposure of the release element ofthe chosen instance of the final dosage form to the selected stimulus.

FIG. 14 illustrates an embodiment of the example operational flow 800 ofFIG. 9. The operational flow 800 may include at least one additionaloperation. The at least one additional operation may include anoperation 860, an operation 870, or an operation 890. The operation 860includes receiving the request specifying a dose of a medicament for anindividual animal. The operation 860 may include at least one additionaloperation. The at least one additional operation may include anoperation 862, or an operation 864. The operation 862 (not shown)includes receiving the request specifying an efficacious medicament dosefor an individual animal. The operation 864 (not shown) includesreceiving the request specifying the final dosage form that includes themedicament for an individual animal.

The operation 870 includes verifying the exposure of the release elementof the chosen instance of the final dosage form to the selectedstimulus. The operation 890 includes dispensing the chosen instance ofthe final dosage form after the exposure of the release element of thechosen instance of the final dosage form to the selected stimulus asdescribed above. The operation 890 may include at least one additionaloperation, such as an operation 892. The operation 892 (not shown)includes dispensing the ex vivo exposed instance of the final dosageform in a package bearing an identifier of the individual animal. Forexample, the identifier may include a name, or identification number ofthe animal.

FIG. 15 illustrates an example environment 1000 that includes the animal198, a cross-sectional view of an example final dosage form 1002 foradministering the medicament 190 to the animal 198, and the examplestimulus source 194 operable to emit a stimulus 192. In an embodiment,the final dosage form includes a dosage form having completed amanufacturing or production process. In an embodiment, the final dosageform includes a product, finished tablet, or capsule ready fordistribution to a hospital, pharmacy, or retail store forindividualizing for a particular animal. In an embodiment, the finaldosage form includes a tablet shape, a spherical shape, or anellipsoidal shape. In an embodiment, the final dosage form includes astructure, a particle, or a polymer that is carryable or transportableto the animal by a solid, cream, liquid, or fluid carrier.

The final dosage form 1002 includes an outer layer 1010, a releaseelement 1030, and the medicament 190. The release element is configuredin a medicament-holding state. The release element is modifiable ex vivoto a medicament-discharge state by an exposure to a stimulus,illustrated as the stimulus 192. In an embodiment, ex vivo includesoutside the body of the animal. In an embodiment, ex vivo includes anenvironment outside or away from the body of the animal. In anembodiment, ex vivo includes outside a living organism, such as “invitro.” In an embodiment, ex vivo includes an external or ambientenvironment.

In an embodiment, the stimulus 192 includes at least one of anon-ionizing radiation, an electromagnetic radiation, a magnetic field,an electric field, an energetic stimulus, or a chemical stimulus. In anembodiment, the stimulus includes at least one of a light radiation,terahertz radiation, microwave radiation, or radio wave radiation. In anembodiment, the stimulus includes at least one of a mechanicallyactivatable structure, heat activatable structure, or pressureactivatable structure. In an embodiment, the stimulus includes at leastone of a thermal, acoustic, or ultrasound stimulus. In an embodiment,the stimulus includes at least one of an activation stimulus, or anactuation stimulus.

In an embodiment, the release element 1030 includes a release elementconfigured in a medicament-holding state. In the medicament-holdingstate, the medicament 190 is substantially not bioavailable to theanimal 198 if the final dosage form 1002 is administered to the animal.The release element is modifiable ex vivo to a medicament-dischargestate by an exposure to the stimulus 192. In the medicament-dischargestate, the medicament is substantially bioavailable to the animal if thefinal dosage form is administered to the animal. In an embodiment,substantially not bioavailable to the animal includes having nosubstantial therapeutic or adverse effect on the animal. In anembodiment, bioavailable to the animal includes the medicament beingphysiologically available, absorbable, transportable, usable, orutilizable by the animal. In an embodiment, bioavailable to the animalindicates that a portion of an administered dose of medicament reachesthe systemic circulation. In an embodiment, not bioavailable to theanimal includes the medicament being physiologically not available, notabsorbable, not transportable, not usable, or not utilizable by theanimal.

In an embodiment, the release element 1030 includes a release elementconfigured in a medicament-holding state. In the medicament-holdingstate, the medicament 190 is insubstantially bioavailable if the finaldosage form 1002 is administered to the animal 198. The release elementis modifiable ex vivo to a medicament-discharge state by an exposure tothe stimulus 192. In the medicament-discharge state, the medicament issubstantially bioavailable if the final dosage form is administered tothe animal. In an embodiment, the release element includes a releaseelement configured in a medicament-holding state. In themedicament-holding state, the medicament is substantiallybio-unavailable if the final dosage form is administered to the animal.The release element is modifiable ex vivo to a medicament-dischargestate by an exposure to the stimulus wherein the medicament issubstantially bioavailable if the final dosage form is administered tothe animal. In an embodiment, bio-unavailable includes present but notusable by the animal.

In an embodiment, the release element includes a release element 1030configured in a medicament-holding state. In the medicament-holdingstate, the medicament 190 has a substantially insignificant effect onthe animal 198 if the final dosage form 1002 is administered to theanimal. The release element is modifiable ex vivo to amedicament-discharge state by an exposure to the stimulus. In themedicament-discharge state, the medicament has a substantiallysignificant effect on the animal if the final dosage form isadministered to the animal. In an embodiment, the release elementincludes a release element configured in a medicament-withholding state,and modifiable ex vivo to a medicament-supplying state by an exposure tothe stimulus.

In an embodiment, the release element 1030 includes a release elementconfigured in a medicament-holding state and field-modifiable ex vivo toa medicament-discharge state by an exposure to the stimulus 192. Forexample, the release element may be field modified at a point ofadministration of the final dosage form, such as clinic or hospital, ata pharmacy such as when a pharmacist is filling a prescription thatincludes the final dosage form, or at a residence by a caregiver or by aperson for whom the final dosage form is prescribed. In an embodiment,the release element includes a release element configured in amedicament-holding state and modifiable ex vivo post-manufacture to amedicament-discharge state by an exposure to the stimulus. In anembodiment, the release element includes a release element forming animperforate barrier in a medicament-holding state. The release elementis modifiable ex vivo by an exposure to the stimulus to form a perforatebarrier in a medicament-discharge state. In an alternative embodiment,the release element is modifiable ex vivo by an exposure to the stimulusto form a perforate barrier in a medicament-discharge state to form atleast one discharge pathway.

In an embodiment, the release element 1030 includes a release elementconfigured in a medicament-holding state. The release element ismodifiable ex vivo to a medicament-discharge state by an exposure to thestimulus 192, the stimulus including at least one of light or radiowaves.

In an embodiment, the final dosage form 1002 includes a particle orpolymer implemented release element. In an embodiment, a polymer mayinclude an intelligent polymer having a changeable property that in onestate admits or discharges at least one molecule of medicament and inanother state engages or retains the at least one molecule ofmedicament. An intelligent polymer includes a polymer structurallyresponsive to an externally applied energy or stimulus. In anembodiment, “applied energy” includes both positive and negative energyvalues, i.e. supplying and removing energy. Examples of intelligentpolymers are described in U.S. Pat. No. 7,104,517 to Derand, et al. Inan embodiment, a particle may include a microsphere, polymericmicrosphere, or nanoparticle.

FIG. 16 illustrates an example environment 1100 that illustrates a finaldosage form 1102 having a release element 1130 implemented by acharacteristic response of a particle or a polymeric material 1180 to astimulus such as, the stimulus 192. An example of the particle orpolymeric material is illustrated as a liposome. The final dosage formincludes molecules of the medicament 190 carried by the particle or apolymeric material, again illustrated with respect to the liposome.Example water-soluble drug molecules 190A are illustrated as engaged,retained, or entrapped in an internal aqueous compartment site 1120A.Example lipid-soluble drug molecules 190B are illustrated as engaged,retained or entrapped in a bilayer site 1120B. The example environment1100 illustrates the release element configured in a medicament-holdingstate with at least one molecule of the medicament engaged, retained orentrapped. In an embodiment, the release element has, for example byapplication of a stimulus, such as the stimulus 192, been changed into astate (not shown) that admits at least one molecule of the medicament,illustrated as the water-soluble drug molecules 190A or thelipid-soluble drug molecules 190B. The release element state is changedby withdrawal of the stimulus into a state (shown) that engages, retainsor entraps the water-soluble drug molecules 190A or the lipid-solubledrug molecules 190B. Continuing this example, the release element ismodifiable ex vivo to a medicament-discharge state by an exposure to astimulus, such as the stimulus 192, which may be the same stimulus usedto switch the release element and load the water-soluble drug molecules190A or the lipid-soluble drug 190B into the liposome, or may be anotherstimulus 192. In an alternative of this example, a chemical stimulus maybe used to load the at least one molecule in the liposome, and anotherstimulus, such as an electromagnetic wave used to modify the liposome toa medicament-discharge state.

The characteristic response of the particle or polymeric material to thestimulus 192 may include any characteristic response that releases anengaged, retained, or entrapped medicament 190 from the particle orpolymeric material. For example, a characteristic response of aparticular particle or polymeric material may include a releasingbursting, expanding, cleaving, or degradation of the particular particleor polymeric material in response to a microwave stimulus implements therelease element 1130.

In an embodiment, the release element 1130 is configured in amedicament-holding state. The release element is modifiable ex vivo to amedicament-discharge state by an exposure to the stimulus 192. Therelease element including at least one of a gel, gel matrix, hydrogelfibrin, or a dendrimer. Examples hydrogels are described in Y. Qiu, etal, Enivoronment-sensitive hydrogels for drug delivery, SCIENCEDIRECT(October 2001), citing Triggering in Drug Delivery Systems, 53 ADVANCEDDRUG DELIVERY REVIEWS 321-339 (Issue 3, December 2001). Examplespolymers and dendrimers are described in C. Henry, Drug Delivery, 80CHEMICAL & ENGINEERING NEWS 39-47 (No. 34, Aug. 26, 2002) (The drugs areconjugated to the dendrimers using photocleavable or labile linkers,which can be made to release the drug using light or through acidcleavage). Examples of photo-labile, radio-labile, and enzyme-labiledendrimers are described in U.S. Pat. No. 6,471,968 to Baker, et al.;and in U.S. Pat. No. 7,078,461 to Tomalia, et al. In an embodiment, aparticle or polymeric material having a characteristic responsive to anexposure to the stimulus include an intelligent or environmentallysensitive particle or polymeric material.

In an embodiment, the release element 1130 includes a particle (notspecifically shown) configured in a medicament-holding state. Theparticle is modifiable ex vivo to a medicament-discharge state by anexposure to the stimulus 192. Examples of environmentally sensitiveparticles such as microspheres have been described previously herein. Inan embodiment, the release element includes a polymer substanceconfigured in a medicament-holding state. The polymer substance ismodifiable ex vivo to a medicament-discharge state by an exposure to thestimulus. Examples of environmentally sensitive polymer substances havebeen described previously herein.

Returning to FIG. 15, in an embodiment, the release element 1030includes a non-shape-memory material configured in a medicament-holdingstate. The non-shape-memory material is modifiable ex vivo to amedicament-discharge state by an exposure to the stimulus 192. In anembodiment, the release element includes a release element disposed atleast partially within the outer layer 1010 and configured in amedicament-holding state. The release element is modifiable ex vivo to amedicament-discharge state by an exposure to the stimulus. In themedicament-discharge state the medicament 190 is substantially availablefor an in vivo release into the animal 198 if the final dosage form isadministered to the animal while the release element is configured inthe medicament-discharge state.

In an embodiment, the final dosage form 1002 further includes a chamber1020 located substantially within the outer layer 1010 and carrying themedicament 190. In an embodiment, the chamber 1020 is substantiallysimilar to the chamber 120 described in conjunction with FIG. 1. In anembodiment, the final dosage form further includes the indicator element180 configured to indicate an exposure of the release element 1030 tothe stimulus 192.

Another embodiment provides a final dosage form 1002 for administeringthe medicament 190 to the animal 198. This embodiment of the finaldosage may be illustrated by reference to FIG. 15 and/or by reference toFIG. 16. With reference to an embodiment illustrated by FIG. 15, thefinal dosage form 1002 includes a release element 1030, a site 1020carrying the medicament, the medicament, and a containment element 1040.The release element 1030 is configured in a medicament-holding state andmodifiable ex vivo to a medicament-discharge state by an exposure to thestimulus 192. The containment element retains the medicament within thefinal dosage form until the final dosage form is administered to theanimal. In an embodiment, the containment element may be substantiallysimilar to the containment element 140 described in conjunction withFIG. 1.

With reference to an embodiment illustrated by FIG. 16, an embodiment ofthe final dosage form includes the final dosage form 1102 having arelease element 1130 formed by a particle or polymer 1180, a sitecarrying the medicament 190 (depicted as the internal aqueouscompartment site 1120A or as the bilayer site 1120B), the medicament.The release element is configured in a medicament-holding state andmodifiable ex vivo to a medicament-discharge state by an exposure to thestimulus.

In an embodiment, the final dosage form 1102 includes a containmentelement 1140. The containment element retains the medicament within thefinal dosage form until the final dosage form is administered to theanimal. In an embodiment, the containment element 1140 includes aparticle or polymeric substance retaining the medicament 190 within thefinal dosage form 1102 until the final dosage form is administered tothe animal 198 (not shown). For example, the containment element mayinclude a gel, hydrogel, liposome microsphere, polymeric microsphere,dendrimer, or nanoparticle. In an embodiment, the containment elementmay be another particle or polymer that engages, retains, or entraps theparticle or polymer in a containing manner (not shown). In anembodiment, the containment element may be substantially similar to thecontainment element 140 of the final dosage from 102 described inconjunction with FIG. 1. In an embodiment, the containment element maybe substantially similar to the erodible outer layer 110 of the finaldosage form 102 described in conjunction with FIG. 1. In an embodiment,the release element 1130 and the containment element are at least asubstantially same structure, for example a microsphere. In anembodiment, the release element and the containment element aresubstantially different structures, for example a microspherecontainment element containing a dendrimer release element. In anembodiment, the containment element includes a carrier, excipient,diluent, or admixture retaining the medicament within the final dosageform until the final dosage form is administered to the animal.

In an embodiment, the site 1120 carrying the medicament 190 includes achamber carrying the medicament. In an embodiment, the site carrying themedicament includes a region carrying the medicament. In an embodiment,the site carrying the medicament includes a binding site releasablycarrying the medicament. In an embodiment, the site carrying themedicament includes the release element 1130 or a particle or polymericmaterial carrying the medicament. In an embodiment, the site carryingthe medicament includes a binding site releasably carrying themedicament.

In an embodiment, the final dosage form includes an indicator element180 configured to indicate an exposure of the release element to thestimulus. With reference to an embodiment illustrated by FIG. 15, thefinal dosage form 1002 includes an indicator element 180 configured toindicate an exposure of the release element 1030 to the stimulus 192.With reference to FIG. 16, the final dosage form 1102 includes anindicator element (not shown) configured to indicate an exposure of therelease element 1130 to the stimulus 192.

FIG. 17 illustrates an example environment 1200 that includes an article1201. The article includes at least one final dosage form foradministering a therapeutically effective amount of a medicament to ananimal. In an embodiment, the final dosage form includes a final dosage1202 that is substantially similar to the final dosage form 1002described in conjunction with FIG. 15. In an embodiment, the finaldosage form includes the final dosage form 1202 that is substantiallysimilar to the final dosage form 1102 described in conjunction with FIG.16 (not shown in FIG. 17). The final dosage form of FIG. 17 includes anouter layer 1210, a release element 1230, a site 1220 carrying themedicament 190. The release element includes a release elementconfigured in a medicament-holding state. The release element ismodifiable ex vivo to a medicament-discharge state by an exposure to thestimulus 192. The article also includes instructions 1270 for theexposure of the release element to the stimulus sufficient to modify therelease element to the medicament-discharge state. In an embodiment, theinstructions include instructions specifying the exposure of the releaseelement to a human-initiated stimulus sufficient to modify the releaseelement to the medicament-discharge state. In an embodiment, theinstructions include instructions specifying the exposure of the releaseelement to provide an automatically-initiated stimulus sufficient tomodify the release element to the medicament-discharge state.

FIG. 18 illustrates an example operational flow 1300 modifying amedicament availability characteristic of a final dosage form. A startoperation occurs in an environment 1305 that includes the final dosageform. The final dosage form includes an outer layer, a release element,a site carrying the medicament, and the medicament. The release elementis configured in a medicament-holding state wherein a medicament issubstantially not bioavailable to the animal, such as the animal 198.The release element is modifiable ex vivo to a medicament-dischargestate by an exposure to the stimulus wherein the medicament issubstantially bioavailable to the animal. In an embodiment, the finaldosage form is substantially similar to the final dosage form 1002described in conjunction with FIG. 15. In an embodiment, the finaldosage form is substantially similar to the final dosage form 1102described in conjunction with FIG. 16

After the start operation, the operational flow 1300 includes anactivating operation 1310. The activating operation includes initiatingan exposure of a release element of the final dosage form to a stimulus,such as the stimulus 192. The initiated stimulus is selected totransform the release element from a medicament-holding state to amedicament-discharge state. In an embodiment, the initiated stimulusincludes an initiated stimulus having a parameter selected to transformthe release element from a medicament-holding state to amedicament-discharge state. In an embodiment, the initiated stimulusincludes an initiated stimulus having at least one of a stimulationcharacteristic or a spatial characteristic selected to transform therelease element from a medicament-holding state to amedicament-discharge state. In an embodiment, the initiating an exposureof a release element of the final dosage form to a stimulus includesinitiating a first exposure of a release element of the final dosageform to a stimulus. The initiated first stimulus is selected totransform the release element from a medicament-holding state to amedicament-discharge state. This embodiment further includes receivingan indication of the first exposure of the release element of the finaldosage form to the stimulus, the indication generated in response to anindicator element of the final dosage form configured to indicate anexposure of the release element to the stimulus. This embodiment furtherincludes initiating a second exposure of the release element of thefinal dosage form to the stimulus. The initiated second exposurestimulus is selected to further transform the release element from themedicament-holding state to the medicament-discharge state.

In an embodiment, the final dosage form includes a containment elementretaining the medicament within the final dosage form until the finaldosage form is introduced into the animal. In an embodiment, the finaldosage form includes an indicator element configured to indicate anexposure of the release element to the stimulus.

FIG. 19 illustrates an example final dosage form 1400 for administeringa medicament to an animal. The final dosage includes means 1410 forprotecting the final dosage form from an ex vivo environment. The finaldosage form includes means 1420 for releasing the medicament, configuredin a medicament-holding state, and modifiable ex vivo to amedicament-discharge state by an exposure to a stimulus, such as thestimulus 192. The final dosage form includes the medicament 1430.

In an embodiment, the final dosage form includes means 1440 for carryingthe medicament. In an embodiment, the means 1440 for carrying themedicament is positioned substantially within the means 1410 forprotecting the final dosage form. In an embodiment, the final dosageform includes means 1450 for indicating an exposure of the means forreleasing the medicament to the stimulus. In an embodiment, the finaldosage form includes means 1460 for containing the medicament within thefinal dosage form until the final dosage form is introduced into theanimal.

An embodiment provides a final dosage form for administering amedicament to an animal. In this embodiment, the final dosage formincludes at least one particle or polymeric material respectivelycarrying at least one molecule of the medicament. The particle orpolymeric material is configured in a medicament-retention state whereinthe medicament is substantially not bioavailable to the animal if thefinal dosage form is administered to the animal. The particle orpolymeric material is modifiable ex vivo by an exposure to the stimulusto a medicament-release state wherein the medicament is substantiallybioavailable to the animal if the final dosage form is administered tothe animal. This embodiment is described, for example, by reference toFIG. 16, FIG. 20, and/or FIG. 21. In an embodiment, the particle orpolymeric material may include at least one of the particle or polymericmaterials previously described. In an embodiment, the particle orpolymeric material includes an intelligent particle or polymericmaterial. In an embodiment, the particle or polymeric material includesa polymer matrix structure responsive to the exposure to a stimulus. Inan embodiment, the particle or polymeric material includes at least oneof a microparticle, a gel or a dendrimer based microparticle responsiveto the exposure to a stimulus. In an embodiment, the particle orpolymeric material includes at least one of a noisome, fibrin, polymericmicelle, microsome, cyclodextrin, polymer-medicament conjugate, orcellulose responsive to the exposure to a stimulus. In an embodiment,the particle or polymeric material includes at least one of a gel, a gelmatrix, a natural gel, a synthetic gel, a colloid gel, or a hydrogelstructure covalently bonded to the medicament using a photo labile bondand responsive to the exposure to a stimulus. A synthetic gel mayinclude cellulose or polymers. In an embodiment, the particle orpolymeric material includes at least one of a dendrimer, dendrimsome,dendromsome, dendron (partial dendrimer), or dendriplex material. In anembodiment, the particle or polymeric material includes at least one ofan emulsion, nano-emulsion, or double emulsion. In an embodiment, theparticle or polymeric material includes at least one of a lipid,cationic lipid, lipid micelle, liposome, lipospheres, acousticallyactive lipospheres, acoustically-active microbubbles conjugated toliposomes, lipid-coated microbubbles, cerasomes, magnetic liposomes,metallosomes, or a mimetic. Acoustically-active microbubbles conjugatedto liposomes are described in A. Kheirolomoom, et al.,Acoustically-active microbubbles conjugated to liposomes:characterization of a proposed drug delivery vehicle, J. CONTROL RELEASE118(3) (Apr. 23, 2007):275-84; Epub 2006 Dec. 23. A cerasomes mayinclude liposomes with a silicate surface. A mimetic may include anartificial micelle or membrane.

FIG. 20 illustrates an example environment 1500 that includes a finaldosage form 1502 configurable to administer a medicament to the animal198. The final dosage form includes at least one molecule of themedicament 190. The final dosage form also includes at least one of aparticle or polymeric material 1580, which is depicted as a gel. Theparticle or polymeric material has a characteristic response 1530 to thestimulus 192 that releases an engaged, retained, or entrapped at leastone molecule of the medicament 190 from the particle or polymericmaterial. For example, a characteristic response of a particularparticle or polymeric material may include a releasing bursting,expanding, cleaving, or degradation of the particular particle orpolymeric material in response to a microwave stimulus.

The at least one particle or polymeric material 1580 respectivelycarries the at least one molecule of the medicament 190. The particle orpolymeric material is configured in a medicament-retention state whereinthe medicament is substantially not bioavailable to the animal 198 ifthe final dosage form is administered to the animal. The particle orpolymeric material being modifiable ex vivo by an exposure to thestimulus 192 to carry the medicament in a medicament-release statewherein the medicament is substantially bioavailable to the animal ifthe final dosage form is administered to the animal.

FIG. 21 illustrates an example environment 1600 depicting retention andrelease states of particle or polymeric material 1680 (depicted as ahydrogel) carrying the medicament 190 and responsive to an ex vivostimulus 192. FIG. 21A illustrates a medicament-release state where twoinstances of the medicament, collectively labeled “190 Released,” havebeen released from the particle or polymeric material in amedicament-release state. FIG. 21B illustrates a medicament-retentionstate where two instances of the medicament, collectively labeled “190Retained” are carried by the particle or polymeric material in amedicament-retention state. Application of the stimulus ex vivo to theparticle or polymeric material switches it from the medicament-retentionstate to the medicament-release state. For example, an ex vivoapplication of the stimulus to the hydrogel switches it from a pore“closed” state 1630-C to a pore “open” state 1630-O.

Returning to FIG. 16, FIG. 16 illustrates the particle or polymericmaterial 1180, which is depicted as a liposome. The particle orpolymeric material carries the medicament 190. The particle or polymericmaterial is configured in a medicament-retention state wherein themedicament is substantially not bioavailable to the animal if the finaldosage form is administered to the animal 198. The particle or polymericmaterial is modifiable ex vivo by an exposure to the stimulus 192 tocarry the medicament in a medicament-release state wherein themedicament is substantially bioavailable to the animal if the finaldosage form is administered to the animal.

Returning to FIG. 20, in an embodiment, the medicament 190 includes apharmacologically-active agent. In an embodiment, the medicamentincludes at least one of an agent, treatment agent, drug, prodrug,therapeutic, nutraceutical, medication, vitamin, nutritional supplement,medicine, remedy, medicinal substance, or cosmetic.

In an embodiment, the particle or polymeric material 1580 carrying themedicament 190 includes a particle or polymeric material conjugated withthe medicament. In an embodiment, the particle or polymeric materialcarrying the medicament includes a particle or polymeric materialcontaining, intertwined, or bound with the medicament. In an embodiment,the particle or polymeric material carrying the medicament includes aparticle or polymeric material entrapping the medicament.

In an embodiment, the particle or polymeric material 1180 carrying themedicament 190 includes a particle or polymeric material carrying themedicament 190 and configured in a medicament-withholding state. In themedicament-withholding state the medicament is substantially notbioavailable to the animal 198 if the final dosage form 1102 isadministered to the animal 198. The particle or polymeric material ismodifiable ex vivo by an exposure to the stimulus 192 to carry themedicament in a medicament-supplying state wherein the medicament issubstantially bioavailable to the animal if the final dosage form isadministered to the animal. In an embodiment, the particle or polymericmaterial includes a particle or polymeric material carrying themedicament and configured in a medicament-retention state. In themedicament-retention state the medicament is substantially notbioavailable to the animal if the final dosage form is administered tothe animal. The particle or polymeric material is modifiable ex vivoupon at least one of a post-manufacture or a field exposure to thestimulus to a medicament-release state. In medicament-release state, themedicament is substantially bioavailable to the animal if the finaldosage form is administered to the animal. In an embodiment, theparticle or polymeric material includes a particle or polymeric materialcarrying the medicament and configured in a medicament-holding state. Inthe medicament-holding state the medicament is substantially notbioavailable to the animal if the final dosage form is administered tothe animal. The particle or polymer material is modifiable ex vivo to anin vivo release-facilitation state by an exposure to the stimulus to amedicament-release state. In the in vivo release-facilitation state themedicament is substantially bioavailable to the animal if the finaldosage form is administered to the animal.

In an embodiment, the particle or polymeric material 1580 includes aparticle or polymeric material having a premodification characteristicthat results in an insignificant uptake of the particle or polymericmaterial in the gastrointestinal tract of the animal 198. In anembodiment, the particle or polymeric material includes an intactparticle or polymeric material having a premodification characteristicthat results in an insignificant uptake of the particle or polymericmaterial in the gastrointestinal tract of the animal. In an embodiment,the particle or polymeric material includes at least one of a gel, gelmatrix, or hydrogel structure covalently bonded to the medicament usinga photo labile bond. An example of a medicament covalently bonded to ahydrogel using photo labile bonds, and the medicament is not be releasedunless the gel matrix is exposed to enough light to break the bonds isdescribed in U.S. Pat. No. 6,985,770 to Nyhart, Jr. An example of amedicament conjugated to dendrimers using photocleavable or labilelinkers, which can be made to release the drug using light or throughacid cleavage is described in Y. Qiu, supra., and C. Henry, supra. In anembodiment, the particle or polymeric material includes at least one ofa dendrimer, dendrimsome, or dendriplex material. Examples ofphoto-labile, radio-labile, and enzyme-labile dendrimers are describedin U.S. Pat. No. 6,471,968 to Baker, et al.; and examples of photolabile biocompatible dendrimers made from poly(propyleneimine) (POPAM)interiors and poly(amidoamine) (PAMAM) are described in U.S. Pat. No.7,078,461 to Tomalia, et al.

In an embodiment, the particle or polymeric material 1580 includes aliposome carrier entrapping the medicament and having an intact particlesize resulting in an insignificant uptake in the gastrointestinal tractof the animal 198. In an embodiment, the particle or polymeric materialincludes a liposome carrier having a particle size of at leastapproximately three microns. An example of a liposome carrier having aparticle size of at least approximately three microns resulting aninsignificant uptake in the gastrointestinal tract of the animal isdescribed in D. Deshmukh, Can intact liposomes be absorbed in the gut?LIFE SCI. 1981 Jan. 19; 28(3):239-42; See also, MARC J. OSTRO,LIPOSOMES: FROM BIOPHYSICS TO THERAPEUTICS 140 (1987); 42 J. PHARMACYAND PHARMACOLOGY 821-826 (1990); 86 INTER. J. PHARMACY 239-246 (1992);PHARMACEUTICAL PARTICULATE CARRIERS: THERAPEUTIC APPLICATIONS Ch. 4 (p.65, and FIGS. 15 and 16 at page 92) (edited By Alain Rolland 1993). Inan embodiment, the particle or polymeric material includes a liposomehaving a particle size of at least approximately four microns.

In an embodiment, the particle or polymeric material 1580 includes atleast one of a nanoparticle, a microsphere, or a polymeric microsphereresponsive to the exposure to the stimulus 192. In an embodiment, theparticle or polymeric material includes a pharmaceutically-acceptableinert particle or polymeric material.

In an embodiment, the stimulus 192 includes a non-ionizing radiationstimulus. In an embodiment, the stimulus includes an electromagneticradiation stimulus. In an embodiment, the stimulus includes at least oneof a light radiation, terahertz radiation, microwave radiation, andradio wave radiation stimulus. In an embodiment, the stimulus includes amagnetic stimulus. In an embodiment, the stimulus includes an electricstimulus. In an embodiment, the stimulus includes an energetic stimulus.In an embodiment, the stimulus includes a chemical stimulus. In anembodiment, the stimulus includes at least one of a mechanical, heat, orpressure stimulus. In an embodiment, the stimulus includes at least oneof an activation stimulus, or an actuation stimulus. In an embodiment,the stimulus includes at least one of at least one of a thermal,acoustic, or ultrasound stimulus. In an embodiment, the stimulusincludes a stimulus facilitating a release of the medicament by at leastone of an expansion of a gel, gel matrix, or hydrogel carrier. In anembodiment, the stimulus includes a stimulus facilitating a release ofthe medicament by at least one of an expansion of a gel, gel matrix, orhydrogel carrier to allow a diffusion and bioavailability of themedicament. In an embodiment, the stimulus includes a stimulusfacilitating the release of the medicament from the particle orpolymeric carrier by at least one of a bursting of a liposome material,formation of a pore in a liposome material, or an unpacking of theparticle or polymeric material.

In an embodiment, the particle or polymeric material 1580 includes aparticle or polymeric material carrying the medicament 190 andconfigured in a medicament-retention state wherein the medicament issubstantially not bioavailable to the animal 198 if the final dosageform is administered to the animal. The particle or polymeric materialmodifiable ex vivo by an exposure to the stimulus 192 to carry themedicament in a medicament-release state allowing an in vivo release ofthe medicament if the final dosage form is administered to the animal.

In an embodiment, the particle or polymeric material 1580 includes afirst particle or polymeric material carrying the medicament 190, and asecond particle or polymeric material (not shown) carrying the firstparticle or polymeric material. The second particle or polymericmaterial is configured in a first particle or polymericmaterial-retention state wherein the first particle or polymericmaterial is substantially not bioavailable to the animal if the finaldosage form is administered to the animal 198. The second particle orpolymeric material is modifiable ex vivo by an exposure to the stimulus192 to carry the medicament a first particle or polymericmaterial-release state wherein the first particle or polymeric materialis substantially bioavailable to the animal if the final dosage form isadministered to the animal.

In an embodiment, the final dosage form 1502 further includes atransport medium 1560 suitable for administering the particle orpolymeric material 1580 carrying the medicament to the animal 198. Forexample, the transport medium may include a carrier, admixture, diluent,or excipient. In another example, the transport medium may include apolymer, such as a hydrogel. An example of a polymer transport medium isdescribed in United States Patent Application Pub. 2008/0050445 byAlcantar. In an embodiment, the final dosage form further includes anindicator substance (not illustrated) configured to indicate an exposureof the particle or polymeric substance to the stimulus 192. In anembodiment, the final dosage form further includes an indicatorsubstance (not illustrated) configured to visually indicate an exposureof the particle or polymeric substance to the stimulus 192.

An embodiment includes the final dosage form for administering themedicament 190 to the animal 198. In this embodiment, the final dosageform includes the medicament and a particle or polymeric material. Theparticle or polymeric material carries the medicament. The particle orpolymeric material is configured in a medicament-retention state whereinthe medicament is substantially not bioavailable to the animal if thefinal dosage form is administered to the animal. The particle orpolymeric material is modifiable ex vivo by an exposure to a firststimulus to carry the medicament a first medicament-release statewherein the medicament has a first bioavailability to the animal if thefinal dosage form is administered to the animal. The particle orpolymeric material is modifiable ex vivo by an exposure to a secondstimulus to carry the medicament in a second medicament-release statewherein the medicament has a second bioavailability to the animal if thefinal dosage form is administered to the animal. Understanding of thisembodiment may be facilitated by reference to the preceding descriptionin conjunction with FIG. 16, FIG. 20, or FIG. 21.

In an embodiment, the first bioavailability includes a first deliveryrate of the medicament and the second bioavailability includes a seconddelivery rate of the medicament. For example, the particle or polymericmaterial may have a characteristic that include an adjustable pore sizeresponsive to a temperature of the particle or polymeric materialattained in response to a heat stimulus. The heat stimulus may include amicrowave or a light source. The first stimulus may include an exposureof the particle or polymeric material to a first temperature, or to agiven temperature for a first period of time. The second stimulus mayinclude an exposure of the particle or polymeric material to a secondtemperature, or to a given temperature for a second period of time. Forexample, selective control of temperature-modulatable materials isdescribed in G. Rao, et al., Synthesis of Smart Mesoporous Materials,MRS BULLETIN P7.8 (Spring 2003). For example, an adjustable porosity ofan organic polymer membrane is described in R. Estrada, et al., Smartpolymeric membranes with adjustable pore size, 52 International journalof polymeric materials 833-843 (No. 9, 2003). For example, athermosensitive grafted polymeric system which can be triggered torelease the loaded drug with an increase in temperature, induced by amagnetic thermal heating event, is described in I. Ankareddi, et al.,Development of a Magnetically Triggered Drug Delivery System usingThermoresponsive Grafted Polymer Networks with Magnetic Nanoparticles, 2NANOTECH 431-434 (Vol. 2, 2007). See also, R. Liburdy, et al.,Microwave-triggered liposomal drug delivery: investigation of a modeldrug delivery system, Engineering in Medicine and Biology Society1163-1164, (Vol. 4, November 1989) (Images of the Twenty-First Century,Proceedings of the Annual International Conference of the IEEEEngineering). In another example, the first stimulus may include a firstultrasound power density and the second stimulus may include a secondultrasound power density. For example, bioavailability of polymericmicelles as a variable function of ultrasound power density is at leastsuggested by A. Marin, et al., Acoustic activation of drug delivery frompolymeric micelles: effect of pulsed ultrasound, 71 JOURNAL OFCONTROLLED RELEASE 239-249 (Issue 3, 28 Apr. 2001).

In an embodiment, the final dosage form 1502 configurable to administera medicament to the animal 198 includes a containment element 1540. Inan embodiment, the containment element 1540 may be substantially similarto the containment element 140 described in conjunction with FIG. 1. Inan embodiment, the containment element 1540 includes a pH-sensitivecomponent of a liposome. For example, S. Cho, et al, pH-dependentrelease property of dioleoylphosphatidyl ethanolamine liposomes, 25KOREAN JOURNAL OF CHEMICAL ENGINEERING 390 (No. 2, 2008) describes apH-sensitive liposome prepared by a detergent removal method thatretains at neutral pH (6-8), and releases at pH 5. In an embodiment, thecontainment element includes tunable component of a liposome. Forexample, I. Hafez, et al., Tunable pH-Sensitive Liposomes Composed ofMixtures of Cationic and Anionic Lipids, 79 BIOPHYSICAL JOURNAL 1438(Issue 3, 2000) describes a tunable liposome using cationic and anioniclipid mixtures (cholesteryl hemisuccinate (CHEMS) andN,N-dioleoyl-N,N-dimethylammonium chloride. In an embodiment, thecontainment element includes pH sensitive Chitosan and polyacrylamidecopolymer hydrogels releasing contained substances upon pH changes. Forexample, as described in P. Bonina, et al., 19 JOURNAL OF BIOACTIVE ANDCOMPATIBLE POLYMERS 101 (No. 2, 2004). In an embodiment, the containmentelement includes a pH sensitive Chitosan and polyalkyleneoxide-maleicacid copolymer releasing substances on pH changes. For example, asdescribed in T. Yoshizawa, et al., pH-and temperature-sensitivepermeation through polyelectrolyte complex films composed of chitosanand polyalkyleneoxide-maleic acid copolymer, 241 JOURNAL OF MEMBRANESCIENCE 347 (Issue 2, 2004). In an embodiment, the containment elementincludes an acrylic acid (AA) grafted onto porous polypropylene (PP)producing a pH sensitive membrane. For example, as described in Y. Wang,et al., pH sensitive polypropylene porous membrane prepared by graftingacrylic acid in supercritical carbon dioxide, 45 POLYMER 855 (No. 3,2004).

FIG. 22 illustrates an example environment 1700 that includes an articleof manufacture 1701. The article of manufacture includes at least onefinal dosage form 1702 for administering the medicament 190 to theanimal 198. The final dosage form includes the medicament, a particle orpolymeric material 1780 carrying the medicament, and an instruction1770. In an embodiment, the particle or polymeric material carrying themedicament may include the particle or polymeric material described inconjunction with FIG. 20. In an embodiment, the particle or polymericmaterial carrying the medicament may include a particle or polymericmaterial described in this paper. An embodiment of the particle orpolymeric material carrying the medicament is depicted in FIG. 22 as agel material for illustrative purposes. The particle or polymericmaterial has a characteristic response 1730 to the stimulus 192 thatreleases an engaged, retained, or entrapped at least one molecule of themedicament 190 from the particle or polymeric material. For example, acharacteristic response of a particular particle or microparticle mayinclude a releasing bursting, expanding, cleaving, or degradation of theparticular particle or microparticle in response to a microwavestimulus.

The particle or polymeric material 1780 is in a medicament-retentionstate wherein the medicament is substantially not bioavailable to theanimal 198 after administration of the final dosage form. The particleor polymeric material is modifiable ex vivo to a medicament-releasestate by an exposure to the stimulus 192 wherein the medicament issubstantially bioavailable to the animal after administration of thefinal dosage form.

The instruction 1770 includes an instruction for the exposure of theparticle or polymeric material 1780 to a human-initiated stimulus 192sufficient to transform the particle or polymeric material to allow adischarge of at least a portion of the therapeutically effective amountof the medicament from the particle or polymeric carrier.

In an embodiment, the article of manufacture 1701 further includes alabel associated with the at least one final dosage form 1702 or aninsert into a package 1760 containing the at least one final dosageform, the insert providing the instructions 1770. In an embodiment, thefinal dosage form further includes a transport medium 1765 suitable foradministering the particle or polymeric material 1780 carrying themedicament 190 to the animal 195. In an embodiment, the final dosageform further includes an indicator substance (not shown) configured toindicate an exposure of the particle or polymeric material to thestimulus 192.

FIG. 23 illustrates an example environment 1800 that includes a finaldosage form 1802 for administering the medicament 190 to the animal 198.The final dosage form includes at least one molecule of the medicamentand a particle or polymeric carrier 1880, is depicted as a gel, andwhich is operable to bind the at least one molecule of the medicament.The particle or polymeric carrier is configured in a firstmedicament-bioavailability state, and modifiable ex vivo to a secondmedicament-bioavailability state by an exposure to a stimulus,illustrated as the stimulus 192. In an embodiment, the particle orpolymeric carrier operable to bind the at least one molecule of themedicament has a characteristic response 1830 to a stimulus, such as thestimulus 192, that releases the bound at least one molecule of themedicament 190 from the particle or polymeric carrier. An example ofsuch characteristic response is described in conjunction with FIG. 21.In another embodiment, the particle or polymeric carrier operable tobind the at least one molecule of the medicament has a characteristicresponse 1830 to a stimulus, such as the stimulus 192, that unbinds orreleases the at least one molecule of the medicament 190 from theparticle or polymeric carrier.

In an embodiment, the particle or polymeric carrier 1880 includes apharmaceutically-acceptable inert particle or polymeric carrier operableto bind the at least one molecule of the medicament 190. In anembodiment, the particle or polymeric carrier includes a particle orpolymeric carrier operable to engage, retain, or entrap at least onemolecule of the medicament.

In an embodiment, the first medicament-bioavailability state isconfigured to retard medicament release in vivo and the secondmedicament-bioavailability state is configured to allow medicamentrelease in vivo. In an embodiment, the first medicament-bioavailabilitystate is configured to allow medicament release in vivo and the secondmedicament-bioavailability state is configured to retard medicamentrelease in vivo.

In an embodiment, the particle or polymeric carrier 1860 includes aliposome carrier operable to bind the at least one molecule of themedicament 190 and having an intact particle size resulting in aninsignificant uptake in the gastrointestinal tract of the animal 198. Inan embodiment, liposome carrier operable to bind the at least onemolecule of the medicament and having an intact particle size resultingin an insignificant uptake in the gastrointestinal tract of the animalincludes a liposome carrier operable to bind the at least one moleculeof the medicament and having an intact particle size of at leastapproximately one micron. For a description of an example, see, P. Hoet,et al., Nanoparticles—known and unknown health risks, 2 JOURNAL OFNANOBIOTECHNOLOGY 12, at section 4 (2004). In an embodiment, theliposome carrier operable to bind the at least one molecule of themedicament and having an intact particle size resulting in aninsignificant uptake in the gastrointestinal tract of the animalincludes a liposome carrier operable to bind the at least one moleculeof the medicament and having an intact particle size of at leastapproximately three microns. In an embodiment, the liposome carrieroperable to bind the at least one molecule of the medicament and havingan intact particle size resulting in an insignificant uptake in thegastrointestinal tract of the animal includes a liposome carrieroperable to bind the at least one molecule of the medicament and havingan intact particle size of at least approximately four microns.

In an embodiment, the final dosage form 1802 further includes atransport medium 1860 suitable for administering to the animal 198 theparticle or polymeric carrier 1880 holding the at least one molecule ofthe medicament 190. In an embodiment, the final dosage form of claimfurther includes an indicator substance (not shown) configured tovisually indicate an exposure of the particle or polymeric carrierholding the at least one molecule of the medicament to the stimulus 192.

In an embodiment, the final dosage form 1802 configurable to administera medicament 190 to the animal 198 includes a containment element 1840.In an embodiment, the containment element 1840 may be substantiallysimilar to the containment element 140 described in conjunction withFIG. 1. In an embodiment, the containment element 1840 may besubstantially similar to the containment element 1540 described inconjunction with FIG. 20.

FIG. 24 illustrates an example environment 1900 that includes a finaldosage form 1905 and an operational flow 1910. The final dosage formincludes the medicament and a particle or polymeric material. Theparticle or polymeric material carries the medicament in themedicament-retention state wherein the medicament is substantially notbioavailable if the final dosage form is administered to the animal,such as the animal 198. The particle or polymeric material istransformable to the medicament-release state by the exposure to astimulus, such as the stimulus 192, wherein the medicament issubstantially bioavailable if the final dosage form is administered tothe animal. In an embodiment, the final dosage form is at least similarto the final dosage form 1102 described in conjunction with FIG. 16. Inan embodiment, the final dosage form is at least similar to the finaldosage form 1502 described in conjunction with FIG. 20. In anembodiment, the final dosage form may is least similar to the finaldosage form 1802 described in conjunction with FIG. 23. After a startoperation, the operational flow includes an activation operation 1920.The activation operation includes initiating an exposure of the particleor polymeric material of the final dosage form to a stimulus, such asthe stimulus 192 previously described. The initiated stimulus isselected to transform the particle or polymeric material from themedicament-retention state to the medicament-release state.

In an embodiment, the final dosage form 1905 further includes acontainment element retaining the medicament within the final dosageform until the final dosage form is introduced into the animal. In anembodiment, the final dosage form further includes an indicator elementconfigured to indicate an exposure of the particle or polymeric materialto the stimulus.

FIG. 25 illustrates alternative embodiments of the activation operation1920 of FIG. 24. The activation operation may include an operation 1922,an operation 1924, or an operation 1926. The operation 1922 includes aninitiated stimulus having a parameter selected to transform the particleor polymeric material from a medicament-retention state to amedicament-release state. The operation 1924 includes an initiatedstimulus having at least one of a stimulation characteristic or aspatial characteristic selected to transform the particle or polymericmaterial from a medicament-retention state to a medicament-releasestate. The operation 1926 includes initiating a first exposure of aparticle or polymeric material of the final dosage form to a stimulus,the first initiated stimulus selected to transform the particle orpolymeric material from a medicament-retention state to amedicament-release state. The operation 1926 also includes receiving anindication of the first exposure of the release element of the finaldosage form to the stimulus, the indication generated in response to anindicator element of the final dosage form configured to indicate anexposure of the release element to the stimulus. The operation 1926further includes initiating a second exposure of the release element ofthe final dosage form to the stimulus, the initiated second exposurestimulus selected to further transform the release element from themedicament-holding state to the medicament-discharge state.

FIG. 26 illustrates an example embodiment of a final dosage form 2002for administering a medicament, such as the medicament 190 as previouslydescribed, to an animal, such as the animal 198 as previously described.The final dosage form includes means 2010 for entrapping at least onemolecule of the medicament. The final dosage form also includes means2020 for controlling an availability of the entrapped at least onemolecule of medicament, wherein the entrapped at least one molecule ofmedicament is initially substantially not bioavailable if the finaldosage form is administered to the animal. The availability of theentrapped medicament is modifiable ex vivo by an exposure to a stimulus,such as the stimulus 192 described above, to be substantiallybioavailable if the final dosage form is administered to the animal. Thefinal dosage form further includes means 2030 for protecting the means2010 for entrapping at least one molecule of the medicament from an exvivo environment of the final dosage form. The final dosage form alsoincludes the medicament 190.

In an embodiment, the means 2020 for controlling an availability of theentrapped at least one molecule of medicament includes means 2022 forcontrolling an availability of the entrapped at least one molecule ofmedicament and having a premodification characteristic resulting in aninsignificant uptake in the gastrointestinal tract of the animal. In anembodiment, the final dosage form further includes means 2050 forindicating an exposure to the stimulus by the means for controlling anavailability of the entrapped at least one molecule of medicament. In anembodiment, the final dosage form further includes means 2060 forcontaining the medicament within the final dosage form before the finaldosage form is administered to the animal. In an embodiment, the finaldosage form further includes means 2070 for carrying the final dosageform into the animal.

FIG. 27 illustrates an example system 2100. The system includes a finaldosage form holder 2110 configured to carry at least one instance of afinal dosage form, illustrated as final dosage form holder portions2102A-2102C. The system also includes the stimulus source 194 having atleast one controllable stimulus parameter or characteristic, operable togenerate the stimulus 192, and configured to direct the stimulus towardat least a portion of the final dosage form holder. In an embodiment,the stimulus generator is operable to direct the stimulus toward aselectable portion of the final dosage form holder, such as the portion2102A, or a portion of the portion 2102A. The system further includes astimulation controller 2140 operable to regulate a controllableparameter of the stimulus source. In an embodiment, the stimulationcontroller is operable to regulate the controllable stimulus parameterby regulating the stimulus source, by regulating a stimulus transmissionpathway between the stimulus source and the final dosage form holder, orby regulating which spatial portion of the dosage form receives thestimulus.

The system 2100 also includes a stimulation initiation circuit 2160operable to initiate a stimulus 192 having a selected stimulus parameteror characteristic in response to a received input. In an embodiment, thestimulation initiation circuit is configured to transmit using the userinterface 2195 a human perceivable indication of an assessed quality orquantity of the stimulus received by a final dosage form. Thestimulation initiation circuit may receive input from a human 2199, suchas pharmacist or health care provider, or from a stimulus assessmentcircuit 2150. The stimulus assessment circuit is operable to monitor thestimulus received by a final dosage form in response to data receivedfrom an indicator monitoring circuit 2120. The indicator monitoringcircuit is operable to monitor an indicator substance portion of the atleast one instance of the final dosage form. In an embodiment, thestimulus assessment circuit is operable to generate a signal usable toprovide a human perceivable indication of the assessed stimulus receivedby a final dosage form via the user interface.

In an embodiment, the system 2100 includes a final dosage formrecognizer circuit 2130 operable to generate data usable indistinguishing a final dosage form. In an embodiment, the systemincludes a release-state selection circuit 2165. In an embodiment, therelease-state selection circuit is responsive to signals indicative of achosen medicament bioavailability of a final dosage form. In anembodiment, the release-state selection circuit is responsive to a human2199 initiated input entered into the user interface 2195. In anembodiment, the system includes a stimulus selection circuit 2170. In anembodiment, the stimulus selection circuit is responsive to datagenerated by the final dosage form recognizer circuit. In an embodiment,the stimulus selection circuit is responsive to a human 2199 initiatedinput.

In an embodiment, the system 2100 includes a computer-readable storagemedium 2180 configured by a final dosage form and stimulus exposuredatabase 2182. The final dosage form and stimulus exposure database mayinclude instructions for modification or state transformation of thefinal dosage form for an efficacious administration to an animal by anexposure of the final dosage form to a stimulus, such as theinstructions 670 of FIG. 6, the instructions 1270 of FIG. 17, or theinstructions 1770 of FIG. 22. The final dosage form and stimulusexposure database may include instructions for modification or statetransformation of the final dosage form for an efficaciousadministration to an animal by an exposure of the final dosage form tothe stimulus, such as electronically published instructions, or such asindicated by a reference book, such as Physician's Desk Reference. Thefinal dosage form and stimulus exposure database may include anelectronically-stored database relating stimuli andmedicament-bioavailability of the final dosage form, acomputer-implemented decision table, a digitally-maintained final dosageform transformation table, or a digital library correlatingmedicament-bioavailability of the final dosage form and stimuli.

In an embodiment, the system 2100 may be used to modify or transform abioavailability of a medicament associated with a final dosage formdescribed herein. For example, the system may be used to modify ortransform a bioavailability of a medicament associated with the finaldosage form 102 described in conjunction with FIG. 1; the final dosageform 202 described in conjunction with FIG. 2; with the final dosageform 302 described in conjunction with FIG. 3; with the final dosageform 402 described in conjunction with FIG. 4; with the final dosageform 502 described in conjunction with FIG. 5; with the final dosageform 602 described in conjunction with FIG. 6; with the final dosageform 1002 described in conjunction with FIG. 15; with the final dosageform 1102 described in conjunction with FIG. 16; with the final dosageform 1202 described in conjunction with FIG. 17; with the final dosageform 1502 described in conjunction with FIG. 20; with the final dosageform 1702 described in conjunction with FIG. 22; or with the finaldosage form 1802 described in conjunction with FIG. 23.

In an embodiment, the system 2100 may be used to implement anoperational flow modifying or transforming a bioavailability of amedicament associated with a final dosage form described herein. Forexample, the system may be used to implement the example operationalflow 700 modulating a medicament-release characteristic of a finaldosage form described in conjunction with FIG. 7; the exampleoperational flow 800 fulfilling a request specifying a dose of amedicament for an individual animal described in conjunction with FIG.9; the example operational flow 1300 modifying a medicament availabilitycharacteristic of a final dosage form described in conjunction with FIG.18; or the example operation flow 1910 described in conjunction withFIG. 24.

FIG. 28 illustrates an example environment 2200. The environmentincludes a final dosage form 2210 for administering the medicament 190to the animal 198. The final dosage form includes a particle orpolymeric 2202 carrying the medicament in a first medicament-releasestate wherein the medicament is available to the animal in a firstbioavailability if the final dosage form is administered to the animal.The particle or polymeric material is modifiable ex vivo by an exposureto a stimulus, such as the stimulus 192 to carry the medicament in asecond medicament-release state wherein the medicament is available tothe animal in a second bioavailability if the final dosage form isadministered to the animal.

The particle or polymeric material may include a gel, illustrated as ahydrogel 2202A, carrying a medicament 190A in a first medicament-releasestate wherein the medicament is available to the animal in a firstbioavailability if the final dosage form is administered to the animal.The particle or polymeric material may include a liposome, illustratedas a liposome 2202B, carrying a medicament 190B in a firstmedicament-release state wherein the medicament is available to theanimal in a first bioavailability if the final dosage form isadministered to the animal. The particle or polymeric material mayinclude a nanoparticle, illustrated as a nanosphere 2202C, carrying amedicament 190C in a first medicament-release state wherein themedicament is available to the animal in a first bioavailability if thefinal dosage form is administered to the animal.

In an embodiment, the first bioavailability to the animal 198 includes afirst bioavailability characteristic to the animal and the secondbioavailability to the animal includes a second bioavailabilitycharacteristic. In an embodiment, the first bioavailabilitycharacteristic includes the medicament 190 having a bioavailability inthe small intestine of the animal, and the second bioavailabilitycharacteristic includes the medicament having a bio availability in thelarge intestine of the animal. In an embodiment, the firstbioavailability characteristic includes the medicament having a firstmedicament quantity available to the animal, and the secondbioavailability characteristic includes the medicament having a secondmedicament quantity available to the animal. For example, the firstmedicament quantity may be 100 mg and the second medicament quantity maybe 200 mg. In an embodiment, the first bioavailability characteristicincludes the medicament having an immediate release medicament quantityavailable to the animal, and the second bioavailability characteristicincludes the medicament having a time-release medicament quantityavailable to the animal. In an embodiment, the first bioavailabilitycharacteristic includes the medicament having a first time-release rate,and the second bioavailability characteristic includes the medicamenthaving a second time-release rate. In an embodiment, the firstbioavailability characteristic includes the medicament having a firstrelease-decay rate medicament release to the animal, and the secondbioavailability characteristic includes the medicament having a secondrelease-decay rate medicament release to the animal. In an embodiment,the first bioavailability characteristic includes the medicament havinga first pH sensitivity, and the second bioavailability characteristicincludes the medicament having a second pH sensitivity.

In an embodiment, the first bioavailability to the animal 198 includes afirst bioavailability characteristic to the animal and the secondbioavailability to the animal includes a second bioavailabilitycharacteristic. In this embodiment, the second bioavailabilitycharacteristic to the animal may include a substantially differentbioavailability characteristic to the animal than the firstbioavailability characteristic to the animal. In an alternative of thisembodiment, the first bioavailability characteristic to the animalincludes a first medicament dosage and the second bioavailabilitycharacteristic to the animal includes a second medicament dosage. Inanother alternative of this embodiment, the first bioavailabilitycharacteristic to the animal includes a first medicament release kineticand the second bioavailability characteristic to the animal includes asecond medicament release kinetic. In a further alternative of thisembodiment, the first bioavailability characteristic to the animalincludes a first medicament release profile and the secondbioavailability characteristic to the animal includes a secondmedicament release profile. In an alternative of this embodiment, thefirst bioavailability characteristic to the animal includes a firstmedicament release rate and the second bioavailability characteristic tothe animal includes a second medicament release rate. In anotheralternative of this embodiment, the first bioavailability characteristicto the animal includes a first medicament release delay time and thesecond bioavailability characteristic to the animal includes a secondmedicament release delay time. In a further alternative of thisembodiment, the first bioavailability characteristic to the animalincludes a first medicament release pH dependence and the secondbioavailability characteristic to the animal includes a secondmedicament release pH dependence.

In an embodiment, the particle or polymeric material 2202 carrying themedicament 190 includes an inert particle or polymeric material carryingthe medicament. In an embodiment, the particle or polymeric materialcarrying the medicament includes a particle or polymeric materialcarrying the medicament in an association. In an embodiment, theparticle or polymeric material carrying the medicament includes aparticle or polymeric material encapsulating the medicament. In anembodiment, the particle or polymeric material carrying the medicamentincludes a particle or polymeric material encompassing the medicament.In an embodiment, the particle or polymeric material carrying themedicament includes a particle or polymeric material at least one ofengaging, retaining, or binding the medicament. In an embodiment, theparticle or polymeric material carrying the medicament includes aparticle or polymeric material carrier conjugated with the medicament.In an embodiment, the particle or polymeric material carrying themedicament includes the medicament taken-up by the particle or polymericmaterial.

In an embodiment, the final dosage form 2210 further includes atransport medium 2280 suitable for delivering the particle or polymericmaterial binding the medicament to the animal. In an embodiment, thetransport medium may include a carrier, admixture, diluent, orexcipient. In an embodiment, the final dosage form includes an indicatorsubstance (not illustrated) associated with the particle or polymericmaterial and configured to indicate an exposure to the stimulus of theparticle or polymeric material carrying the medicament.

FIG. 29 illustrates an example environment 2300. The example environmentincludes a final dosage form 2310 for administering the medicament 190to the animal 198. The final dosage form includes a dosage portionlabeled as “A Portion” carrying a medicament 190A in a firstmedicament-release state wherein the medicament is bioavailable to theanimal if the final dosage form is administered to the animal. In anembodiment, the dosage portion “A” includes a chamber 2320A defining achamber periphery 2322A. The final dosage portion includes anotherdosage portion labeled as “B Portion” carrying another medicament 190Band including a release element 2330B in a first medicament-releasestate wherein the another medicament has a first bioavailability to theanimal if the final dosage form is administered to the animal in thefirst medicament-release state. The release element is modifiable exvivo to second medicament-release state by an exposure to stimulus,wherein the another medicament has a second bioavailability to theanimal if the final dosage form is administered to the animal in thesecond medicament-release state. In an embodiment, the dosage portion“B” includes a chamber 2320B defining a chamber periphery 2322B.

FIG. 30 illustrates an example environment 2400 that includes a finaldosage form 2405 and an operational flow 2410. The final dosage formincludes a medicament. The final dosage form also includes a particle orpolymeric material carrying the medicament in a first medicament-releasestate wherein the medicament is available to the animal in a firstbioavailability if the final dosage form is administered to the animal.The particle or polymeric material is modifiable ex vivo by an exposureto a stimulus to carry the medicament in a second medicament-releasestate wherein the medicament is available to the animal in a secondbioavailability if the final dosage form is administered to the animal.In an embodiment, the final dosage form may be implemented using thefinal dosage form 2210 described in conjunction with FIG. 28.

The operational flow 2410 includes, after a start operation, amodification operation 2420. The modification operation includestransforming the particle or polymeric material to the secondmedicament-release state by initiating an ex vivo exposure of theparticle or polymeric material to the stimulus. The operational flowincludes an end operation. In an embodiment, the modification operation2420 may be implemented using the system 2100 described in conjunctionwith FIG. 27.

FIG. 31 illustrates an example article of manufacture 2502 foradministering medicament to an animal. The article includes means 2510for releasably encompassing a medicament in a first state wherein themedicament is available to the animal in a first bioavailability if thefinal dosage form is administered to the animal. The means forreleasably encompassing the medicament in a first state is modifiable exvivo by an exposure to a stimulus to releasably encompass the medicamentin a second state, wherein the medicament is available to the animal ina second bioavailability if the final dosage form is administered to theanimal. The article also includes the medicament 190.

In an embodiment, the article 2502 includes means 2530 for protectingthe means 2510 for releasably encompassing the medicament in a firststate. In an embodiment, the article includes means 2550 for indicatingan exposure to the stimulus of the means for releasably encompassing themedicament in a first state. In an embodiment, the article includesmeans 2560 for containing the medicament within the final dosage formbefore the final dosage form is administered to the animal. In anembodiment, the article includes means 2570 for carrying the finaldosage form into the animal.

FIG. 32 illustrates an example environment 2600. The environmentincludes a final dosage form 2610 for administering medicament 190 tothe animal 198. The final dosage form includes a release-controlsubstance 2602 carrying the medicament in a first medicament-releasestate wherein the medicament has a first bioavailability to the animalif the final dosage form is administered to the animal. Therelease-control substance is modifiable ex vivo by an exposure to afirst stimulus, such as a first stimulus 192A (not separately shown) ofthe stimulus 192, to carry the medicament in a second medicament-releasestate wherein the medicament has a second bioavailability to the animalif the final dosage form is administered to the animal. Therelease-control substance is modifiable ex vivo by an exposure to secondstimulus, such as a second stimulus 190B (not shown) of the stimulus192, to carry the medicament in a third medicament-release state whereinthe medicament has a third bioavailability to the animal if the finaldosage form is administered to the animal. The final dosage form alsoincludes the medicament 190.

The release-control substance 2602 may include a gel, illustrated as ahydrogel 2602A carrying a medicament 190A in a first medicament-releasestate wherein the medicament is available to the animal in a firstbioavailability if the final dosage form is administered to the animal.The release-control substance may include a liposome, illustrated as aliposome 2602B carrying a medicament 190B in a first medicament-releasestate wherein the medicament is available to the animal in a firstbioavailability if the final dosage form is administered to the animal.The release-control substance may include a nanoparticle, illustrated asa nanosphere 2602C carrying a medicament 190C in a firstmedicament-release state wherein the medicament is available to theanimal in a first bioavailability if the final dosage form isadministered to the animal.

In an embodiment, the first bioavailability to the animal 198 includesthe medicament 190 being substantially not bioavailable to the animal.In an embodiment, the first bioavailability to the animal includes themedicament being substantially bioavailable to the animal. In thisembodiment, the second bioavailability to the animal may include themedicament being substantially bioavailable to the animal, wherein thesecond bioavailability to the animal is substantially different from thefirst bioavailability to the animal. In an embodiment, the secondbioavailability to the animal includes the medicament beingsubstantially not bioavailable to the animal. In an embodiment, thesecond bioavailability to the animal includes the medicament beingsubstantially bioavailable to the animal. In an embodiment, the thirdbioavailability to the animal includes the medicament beingsubstantially not bioavailable to the animal. In an embodiment, thethird bioavailability to the animal includes the medicament beingsubstantially bioavailable to the animal.

In an embodiment, the third bioavailability to the animal 198 includesthe medicament 190 being substantially bioavailable to the animal,wherein the third bioavailability to the animal is substantiallydifferent from the second bioavailability to the animal. For example,the third bioavailability may be substantially different from the secondbioavailability in dosage amount, dosage rate, or dosage profile. In anembodiment, the third bioavailability to the animal includes themedicament being substantially bioavailable to the animal, wherein thethird bioavailability is substantially different from both the firstbioavailability and the second bioavailability. In an embodiment, thefirst bioavailability includes a first bioavailability characteristic,the second bioavailability includes a second bioavailabilitycharacteristic, and the third bioavailability includes a thirdbioavailability characteristic.

In an embodiment, the release-control substance 2602 includes abiocompatible substance. In an embodiment, a biocompatible substanceincludes a substance having a quality of not having toxic or injuriouseffects on biological systems of the animal. In another embodiment, abiocompatible substance includes a substance that does not elicit anyundesirable local or systemic effects in the animal. In an embodiment,the release-control substance includes a release-control substancehaving a modifiable medicament release characteristic. In an embodiment,the release-control substance includes a release-control substancecarrying the medicament 190 in an initial medicament-retention state. Inan embodiment, the release-control substance includes a particle. In anembodiment, the release-control substance includes a polymeric material.In an embodiment, the release-control substance includes a smallmolecule. In an embodiment, the release-control substance includes acapsule structure.

In an embodiment, the second stimulus 192B (not separately shown)includes a substantially different category of stimulus than the firststimulus 192A. In an embodiment, the second stimulus has at least asubstantially different intensity than the first stimulus. In anembodiment, the second stimulus includes a substantially differentduration than the first stimulus. In an embodiment, the second stimulusincludes a substantially different waveform than the first stimulus.

In an embodiment, the release-control substance 2602 includes arelease-control substance modifiable ex vivo by an exposure of a firstportion of the release-control substance to the first stimulus 192A tocarry the medicament in a second medicament-release state. In thisembodiment, the release-control substance includes a release-controlsubstance modifiable ex vivo by an exposure of a second portion of therelease-control substance to the second stimulus 192B to carry themedicament in a third medicament-release state.

In an embodiment, the final dosage form 2610 includes a transport medium2680 configured to facilitate administering the medicament and therelease-control substance to the animal. In an embodiment, the finaldosage form includes an indicator substance (not shown) configured toindicate an exposure of at least a portion of the release-controlsubstance to at least one of the first stimulus or the second stimulus.In an embodiment, the final dosage form includes an in vivo degradablecontainment element (not shown) configured to retain the release-controlsubstance until the final dosage form is administered to the animal.

The following table illustrates several states of an example of thefinal dosage form 2610:

TABLE 1 Example bioavailability configurations 1-3 Bioavailability ofBioavailability of Bioavailability of medicament in a medicament in amedicament in a Release control final dosage form final dosage formfinal dosage form substance state configuration #1 configuration #2configuration #3 First 1 0 0 medicament- release state Modified to 0 1 2second medicament- release state Modified to 2 2 1 third medicament-release state 0 = the medicament is substantially not bioavailable 1 =the medicament is substantially bioavailable 2 = the medicament issubstantially bioavailable in a characteristic substantially differentthat in 1

FIG. 33 illustrates an example environment 2700 that includes an articleof manufacture 2701. The article of manufacture includes a final dosageform 2710 for administering medicament to the animal 198. The finaldosage form includes the medicament 190 (not shown). The final dosageform also includes a release-control substance carrying the medicamentin a first medicament-release state wherein the medicament has a firstbioavailability to the animal if the final dosage form is administeredto the animal. The release-control substance is modifiable ex vivo by anexposure to a first stimulus to carry the medicament in a secondmedicament-release state wherein the medicament has a secondbioavailability to the animal if the final dosage form is administeredto the animal. The release-control substance is modifiable ex vivo by anexposure to a second stimulus to carry the medicament in a thirdmedicament-release state wherein the medicament has a thirdbioavailability to the animal if the final dosage form is administeredto the animal. In an embodiment, the final dosage form includes atransport medium 2780 configured to facilitate administering themedicament and the release-control substance to the animal. In anembodiment, the final dosage form may be substantially similar to thefinal dosage form 2610 described in conjunction with FIG. 32. Thearticle of manufacture also includes instructions 2770 specifying an exvivo exposure of the release-control substance to the first stimulus orto the second stimulus to achieve a selected second medicament releasestate or a selected third medicament-release state.

In an embodiment, the instructions 2770 include instructions specifyingan ex vivo exposure of the release-control substance to a selected firststimulus or to a selected second stimulus, such that when implementedtransform the release-control substance to the selected secondmedicament-release state or the selected third medicament-release state.

FIG. 34 illustrates an example environment 2800 that includes a finaldosage form 2805 and an operational flow 2810. The final dosage formincludes a medicament. The final dosage form also includes arelease-control substance carrying the medicament in a firstmedicament-release state wherein the medicament has a firstbioavailability to the animal if the final dosage form is administeredto the animal. The release-control substance is modifiable ex vivo by anexposure to a first stimulus to carry the medicament in a secondmedicament-release state wherein the medicament has a secondbioavailability to the animal if the final dosage form is administeredto the animal. The release-control substance is modifiable ex vivo by anexposure to second stimulus to carry the medicament in a thirdmedicament-release state wherein the medicament has a thirdbioavailability to the animal if the final dosage form is administeredto the animal. In an embodiment, the final dosage form 2805 issubstantially similar to the final dosage form 2610 described inconjunction with FIG. 32.

After a start operation, the operational flow includes anindividualization operation 2820. The individualization operationincludes transforming the medicament release state of therelease-control substance of the final dosage form 2805 to the secondmedicament-release state or the third medicament-release state byinitiating an ex vivo exposure of the release-control substancerespectively to the first stimulus or the second stimulus. Theoperational flow includes an end operation. In an embodiment, theoperational flow 2810 may be implemented using the system 2100 describedin conjunction with FIG. 27.

FIG. 35 illustrates an alternative embodiment of the individualizationoperation 2820 of FIG. 34. The individualization operation may includeat least one additional operation. The at least one additional operationincludes an operation 2822, or an operation 2824. The operation 2822includes modifying the medicament release state of the release-controlsubstance to the second medicament-release state or the thirdmedicament-release state by initiating an ex vivo exposure of therelease-control substance respectively to the first stimulus or thesecond stimulus. In an embodiment, the operational 2282 may beimplemented using the system 2100 described in conjunction with FIG. 27.The operation 2824 includes transforming the medicament release state ofthe release-control substance to the second medicament-release state orthe third medicament-release state by initiating an ex vivo exposure ofthe release-control substance to a stimulus selected respectively fromthe first stimulus or the second stimulus. In an embodiment, theoperation 2822 may be implemented using the stimulus selection circuit2165 described in conjunction with FIG. 21.

FIG. 36 illustrates an alternative embodiment of the individualizationoperation 2820 of FIG. 34. The individualization operation may includeat least one additional operation. The at least one additional operationincludes an operation 2832, an operation 2834, or an operation 2836. Theoperation 2832 includes initiating an ex vivo exposure of therelease-control substance respectively to a modification stimulusselected from the first stimulus or the second stimulus. The selectedmodification stimulus having a parameter operative to transform therelease-control substance carrying the medicament from the firstmedicament-release state to the second medicament-release state or tothe third medicament-release state. The operation 2834 includesinitiating an ex vivo exposure of the release-control substance to amodification stimulus selected from the first stimulus or the secondstimulus, the selected modification stimulus operative to transform therelease-control substance carrying the medicament from the firstmedicament-release state to the second medicament-release state or fromthe first medicament-release state to the third medicament-releasestate. The operation 2836 includes initiating an ex vivo exposure of therelease-control substance respectively to a stimulus selected from thefirst stimulus or the second stimulus, the selected stimulus having atleast one of a stimulation characteristic or a spatial characteristicoperable to transform the release-control substance carrying themedicament from the first medicament-release state to the secondmedicament-release state or to the third medicament-release state. Forexample, a stimulation characteristic may include a waveform, duration,or intensity. A spatial characteristic may include initiating an ex vivoexposure of a portion of the release-control substance to the stimulus.

The operations 2832, 2834, or 2286 may be implemented using the stimulusselection circuit 2170 described in conjunction with FIG. 21. In anotherembodiment, the operation 3972 may be implemented using a combination ofthe stimulus selection circuit 2170, the computing device 2175, and/orthe final dosage form and stimulus exposure database 2182 described inconjunction with FIG. 21.

FIG. 37 illustrates an alternative embodiment of the operational flow2810 of FIG. 34. The operational flow 2810 may include at least oneadditional operation, such as a choosing operation 2850. The choosingoperation includes selecting a medicament-release state from the secondmedicament-release state and the third medicament-release state inresponse to a chosen medicament bioavailability of the final dosageform. The choosing operation may be implemented using the release-stateselection circuit 2165 described in conjunction with FIG. 27. In anembodiment, the stimulus selection circuit 2170, the computing device2175, and/or the final dosage form and stimulus exposure database 2182(saved on the computer-readable storage medium 2180) may cooperativelyimplement the choosing operation. The choosing operation may include atleast one additional operation, such as an operation 2860. The operation2860 includes selecting a modification stimulus from the first stimulusand the second stimulus in response to the selected medicament-releasestate. The operation 2860 may be implemented using the stimulusselection circuit 2170 described in conjunction with FIG. 27. In anembodiment, the stimulus selection circuit, the computing device 2175,and/or the final dosage form and stimulus exposure database 2182 maycooperatively implement the operation 2860.

FIG. 38 illustrates an example environment 2900 that includes a finaldosage form 2905 and an operational flow 2910. The final dosage formincludes a medicament. The final dosage form also includes arelease-control substance carrying the medicament in amedicament-retention state wherein the medicament is substantially notbioavailable to the animal if the final dosage form is administered tothe animal. The release-control substance is modifiable ex vivo by anexposure to a first stimulus to carry the medicament in a firstmedicament-release state wherein the medicament has a firstbioavailability to the animal if the final dosage form is administeredto the animal. The release-control substance is modifiable ex vivo by anexposure to a second stimulus to carry the medicament in a secondmedicament-release state wherein the medicament has a secondbioavailability to the animal if the final dosage form is administeredto the animal. In an embodiment, the final dosage form 2905 may besubstantially similar to the final dosage form 2610 described inconjunction with FIG. 32.

After a start operation, the operational flow includes a release statechoosing operation 2920. The release state choosing operation includesautomatically selecting a medicament-release state from the firstmedicament-release state and the second medicament-release state basedon a specified medicament bioavailability of the final dosage form. Inan embodiment, the specified medicament bioavailable may be indicated bya physician's prescription, a request by a person to receive the finaldosage form, or a table. In an embodiment, the release state choosingoperation may be implemented using the system 2100 described inconjunction with FIG. 27. For example, the person 2199 may enter aprescription of 500 mg of penicillin into the user interface 2195. Inresponse thereto, the release-state selection circuit 2165 of the systemautomatically selects a medicament-release state to achieve 500 mg ofpenicillin from the first medicament-release state and the secondmedicament-release state based on the specified medicamentbioavailability of the final dosage form. In an embodiment, theselection may be facilitated using the computing device 2175 andinformation provided by the final dosage form, and stimulus exposuredatabase 2182 described in conjunction with FIG. 27.

A stimulus choosing operation 2930 includes automatically selecting astimulus from the first stimulus and the second stimulus in response tothe selected medicament-release state. In an embodiment, the stimuluschoosing operation may be implemented using the system 2100 described inconjunction with FIG. 27. For example, the stimulus selection circuit2170 may implement the stimulus choosing operation. In an embodiment,the stimulus choosing operation may be implemented in part, in whole by,or in cooperation with the computing device 2175, and/or the finaldosage form and stimulus exposure database 2182. A dosage configurationoperation 2940 includes transforming the medicament release state of therelease-control substance by initiating an ex vivo exposure of therelease-control substance to the selected stimulus. In an embodiment,the dosage configuration operation may be implemented using the system2100 described in conjunction with FIG. 27. For example, the stimulusinitiation circuit 2160 may initiate the ex vivo exposure of therelease-control substance to the selected stimulus 192 generated by thestimulus source 194. The operational flow includes an end operation.

FIG. 39 illustrates an example vehicle 3002 for administering amedicament to the animal 198. The vehicle including means 3010 forreleasably encompassing the medicament in a first medicament-releasestate wherein the medicament has a first bioavailability to the animalif the vehicle is administered to the animal. The means for releasablyencompassing the medicament in a first medicament-release state ismodifiable to a second medicament-release state upon an ex vivo exposureto a first stimulus, the medicament in the second medicament-releasestate having a second bioavailability to the animal if the vehicle isadministered to the animal. The means for releasably encompassing themedicament in a first medicament-release state is modifiable to a thirdmedicament-release state upon an ex vivo exposure to a second stimulus,the medicament in the third medicament-release state having a thirdbioavailability to the animal if the vehicle is administered to theanimal. The vehicle also includes the medicament 190.

In an embodiment, the vehicle includes means 3030 for protecting themeans for releasably encompassing the medicament against an ex vivoenvironment. In an embodiment, the vehicle includes means 3050 forindicating an exposure of the means for releasably encompassing themedicament to the first stimulus or the second stimulus. In anembodiment, the vehicle includes means 3060 for containing themedicament within the vehicle before the final dosage form isadministered to the animal. In an embodiment, the vehicle includes means3070 for carrying the vehicle into the animal.

Returning to FIG. 27, FIG. 27 illustrates another example of system2100. The system includes the computer-readable storage medium 2180configured to indicate a stimulus to modify ex vivo a bioavailability ofa medicament carried by a final dosage form based upon a selectedmedicament bioavailability of the final dosage form. The system alsoinclude a holder 2110 configured to establish ex vivo of the animal alocation of a final dosage form to receive the indicated stimulus 192from a stimulus source 194. The system further includes the stimulussource operable to provide the indicated stimulus. The system alsoincludes a stimulation controller 2140 operable to regulate an ex vivoexposure of a final dosage form to the indicated stimulus.

In an embodiment, the computer-readable storage medium 2180 includes acomputer-readable storage medium configured to indicate a stimulus tomodify ex vivo a bioavailability of a medicament carried by a finaldosage form based upon a selected medicament bioavailability of thefinal dosage form. The indicated stimulus includes at least one of atype, time, intensity, wave form, or pulse form characteristic of thestimulus. In an embodiment, the computer-readable storage mediumincludes a computer-readable storage medium configured to indicate astimulus to modify ex vivo a bioavailability of a medicament carried bya final dosage form based upon a selected medicament bioavailability ofthe final dosage form. The computer-readable storage medium is alsoconfigured to indicate another stimulus to modify ex vivo abioavailability of another medicament carried by another final dosageform based upon another selected medicament bioavailability of theanother final dosage form. In an embodiment, the computer-readablestorage medium includes a computer-readable storage medium configured toindicate a stimulus to modify ex vivo a bioavailability of a medicamentcarried by a final dosage form based upon a selected medicamentbioavailability of the final dosage form. The computer-readable storagemediums is also configured to indicate another stimulus to modify exvivo a bioavailability of the medicament carried by a final dosage formbased upon the selected medicament bioavailability of the final dosageform. In an embodiment, the computer-readable storage medium includes acomputer-readable storage medium configured to indicate a stimulus tothat is at least one of sufficient, effective, or operable modify exvivo a bioavailability of a medicament carried by a final dosage formbased upon a selected medicament bioavailability of the final dosageform.

In an embodiment, the computer-readable storage medium 2180 includes acomputer-readable storage medium configured to indicate a stimulus 192operable to modify ex vivo a bioavailability of a medicament carried bya final dosage form based upon a selected medicament bioavailability ofthe final dosage form. In an embodiment, the computer-readable storagemedium includes a computer-readable storage medium configured toindicate a stimulus to substantially modify ex vivo a bioavailability ofa medicament carried by a final dosage form based upon a selectedmedicament bioavailability of the final dosage form. In an embodiment,the computer-readable storage medium includes a computer-readablestorage medium configured to indicate a stimulus to modify ex vivo abioavailability of a medicament carried by a final dosage form basedupon a selected treatment using the final dosage form. In an embodiment,the computer-readable storage medium includes a computer-readablestorage medium configured to indicate a stimulus to modify ex vivo abioavailability of a medicament carried by a final dosage form basedupon a selected efficacious treatment using the final dosage form.

In an embodiment, the holder 2110 includes a holder operable to locate afinal dosage form in a position to receive the indicated stimulus 192from a stimulus source 194 before an administration of the final dosageform to the animal 192. In an embodiment, the holder includes a holderoperable to establish a location of a final dosage form to receive theindicated stimulus from a stimulus source and ex vivo of the animal. Inan embodiment, the holder includes a holder operable to establish exvivo of the animal a location of at least two instance of a final dosageform to receive the indicated stimulus from a stimulus source.

In an embodiment, the stimulus source 194 includes a stimulus device,circuit, module, or generator operable to provide the indicated stimulus192 for a final dosage form. In an embodiment, the stimulus sourceincludes a stimulus source operable to produce the indicated stimulus.In an embodiment, the stimulus source includes a stimulus sourceoperable to generate the indicated stimulus. In an embodiment, thestimulus source includes a stimulus source operable to provide theindicated stimulus to at least two instances of the final dosage form.In an embodiment, the stimulus source includes a stimulus sourceoperable to provide the indicated stimulus. The indicated stimulusincludes at least one of a mechanical stimulus, a non-ionizing radiationstimulus, an ionizing radiation stimulus, a chemical stimulus, anacoustic stimulus, an ultrasound stimulus, a radio wave stimulus, amicrowave stimulus, a light wave stimulus, or a thermal stimulus. In anembodiment, the stimulus source includes a stimulus source operable toprovide an indicated stimulus having at least one controllablecharacteristic. In an embodiment, the stimulus source includes astimulus source operable to provide the indicated stimulus and to directthe provided stimulus at a portion of the location of a final dosageform established by the holder. In an alternative of the thisembodiment, the stimulus source is operable to provide the indicatedstimulus and to direct the provided stimulus at a selectable portion ofthe location of a final dosage form established by the holder. In anembodiment, the stimulus source includes a stimulus source operable toprovide the indicated stimulus for a final dosage form and for anotherfinal dosage form. In an embodiment, the stimulus source includes astimulus source operable to provide the indicated stimulus for at leasttwo instances of a final dosage form.

In an embodiment, the stimulation controller 2140 includes a stimulationcontroller operable to regulate the stimulus source 194 in response to areceived human-initiated activation input. In an embodiment, thestimulation controller includes a stimulation controller operable toregulate the stimulus source in response to a received feedbackdevice-initiated activation input. In an embodiment, the stimulationcontroller includes a stimulation controller operable to regulate thestimulus source in response to a received stimulus-selector initiatedactivation input. In an embodiment, the stimulation controller includesa stimulation controller operable to regulate the stimulus source inresponse to a received activation input indicating a selected stimulus.In an embodiment, the stimulation controller includes a stimulationcontroller operable to regulate the stimulus source in response to theindicated stimulus for a final dosage form and in response to a receivedactivation input. In an embodiment, the stimulation controller includesa stimulation controller device, circuit, module, or programmed deviceoperable to regulate an ex vivo exposure of a final dosage form to theindicated stimulus. In an embodiment, the stimulation controllerincludes a stimulation controller operable to regulate a stimulustransmission pathway between the stimulus source and the holder inresponse to the indicated stimulus for a final dosage form. In anembodiment, the stimulation controller includes a stimulation controlleroperable to regulate the stimulus source and direct the stimulus towarda selected portion of a final dosage form carried by the holder 2110 inresponse to the indicated stimulus for the final dosage form, and inresponse to a received activation input.

In an embodiment, the stimulation controller 2140 includes a stimulationcontroller operable to regulate a duration of the stimulus, a wavecharacteristic of the stimulus, an intensity of the stimulus, a densityof the stimulus, or amplitude of the stimulus source in response to theindicated stimulus for a final dosage form. In an embodiment, the wavecharacteristic may include a pulse form or a dynamic waveform.

In an embodiment, the system 2100 further includes a stimulus assessmentcircuit 2150 operable to monitor an aspect of the indicated stimulus 192provided by the stimulus source 194. In an embodiment, the stimulusassessment circuit includes a stimulus assessment circuit operable tomonitor an aspect of the indicated stimulus received by a final dosageform. In an embodiment, the stimulus assessment circuit includes astimulus assessment circuit operable to monitor at least one of a type,quantity, or a characteristic of the indicated stimulus received by afinal dosage form. In an embodiment, the stimulus assessment circuitincludes a stimulus assessment circuit operable to monitor an aspect ofthe indicated stimulus received by at least a portion of a final dosageform. In an embodiment, the stimulus assessment circuit includes astimulus assessment circuit operable to monitor an aspect of anindicator substance portion of a final dosage form. In an embodiment,the stimulus assessment circuit includes a stimulus assessment circuitoperable to sense a parameter of a final dosage form responsive to theindicated stimulus received by the final dosage form. In an embodiment,the stimulus assessment circuit includes a stimulus assessment circuitoperable to monitor an aspect of the indicated stimulus received by afinal dosage form, and to generate an output indicative of the monitoredaspect of the indicated stimulus received by the final dosage form. Inthis embodiment, the stimulation controller 2140 includes a stimulationcontroller operable to regulate an ex vivo exposure of a final dosageform to the indicated stimulus in response to the generated outputindicative of the monitored aspect of the indicated stimulus received bythe final dosage form. In an alternative embodiment, the stimulusassessment circuit includes a stimulus assessment circuit operable tomonitor an aspect of the indicated stimulus received by a final dosageform, and to generate an output signal indicative of the monitoredaspect of the indicated stimulus received by the final dosage form andreceivable by the stimulation controller 2140. In an embodiment, thestimulus assessment circuit includes a stimulus assessment circuitoperable to generate a signal usable in providing a human perceivableindication of an aspect of the indicated stimulus received by a finaldosage form.

In an embodiment, the system 2100 further includes an indicatormonitoring circuit 2120 operable to generate a signal indicative of astatus of an indicator substance associated with a final dosage form andconfigured to indicate an exposure to the indicated stimulus by thefinal dosage form. In an embodiment, the indicator monitoring circuitincludes an indicator monitoring circuit operable to generate signalindicative of at least one of an exposed, exposed to an extent, or notexposed status of an indicator substance associated with a final dosageform and configured to indicate an exposure to the indicated stimulus bythe final dosage form. In an embodiment, the indicator monitoringcircuit includes an indicator monitoring circuit operable to generate ahuman perceivable indication of a status of an indicator substanceassociated with a final dosage form and configured to indicate anexposure to the indicated stimulus by the final dosage form. In anembodiment, the indicator monitoring circuit includes an indicatormonitoring circuit operable to generate a machine readable signalindicative of a status of an indicator substance associated with a finaldosage form and configured to indicate an exposure to the indicatedstimulus by the final dosage form.

In an embodiment, the system 2100 further includes a stimulus initiationcircuit 2160 operable to initiate the provision of the indicatedstimulus by the stimulation source. In an embodiment, the stimulusinitiation circuit includes a stimulus initiation circuit operable toinitiate the provision of the indicated stimulus by the stimulationsource in response to at least one of a received user input or anautomatically generated instruction. In an embodiment, the stimulusinitiation circuit includes a stimulus selection circuit operable toselect the indicated stimulus for provision by the stimulus source. Inan embodiment, the stimulus initiation circuit includes a stimulusselection circuit operable to select the indicated stimulus forprovision by the stimulus source in response to at least one of areceived user input or in response to an automatically generated input.

In an embodiment, the system 2100 further includes a final dosage formrecognizer circuit 2130 operable to generate data indicative of anidentifying characteristic of a final dosage form. The data indicativeof an identifying characteristic of the final dosage form may beacquired in response to discernable aspect of the final dosage form,such as a bar code, shape, color, or marking.

FIG. 40 illustrates an example system 3100. The system includes means3110 for persistently storing computer-readable information indicativeof a stimulus operable to modify ex vivo a bioavailability of amedicament carried by a final dosage form for administration of themedicament to an animal. The system also includes means 3120 forestablishing ex vivo of the animal a location of the final dosage formto receive the indicated stimulus from a stimulus source. The systemfurther includes means 3130 for providing the indicated stimulus. Thesystem also includes means 3140 for regulating an ex vivo exposure ofthe final dosage form to the indicated stimulus.

In an embodiment, the means 3110 for persistently storingcomputer-readable information includes means 3112 for persistentlystoring computer-readable information indicative of a stimulus to modifyex vivo a bioavailability of a medicament carried by a final dosage formfor administration of the medicament to an animal. The computer-readableinformation indicative of a stimulus based upon a selected medicamentbioavailability of the final dosage form.

FIG. 41 illustrates an example environment 3200. The environmentincludes a final dosage form 3202 for administering medicament to theanimal 198. The final dosage form includes a dosage portion, illustratedas an “A” Portion. The dosage portion has a chamber 3220A carrying amedicament 190A. The dosage portion includes a release element 3230A ina first medicament-release state. In the first medicament state, themedicament has a first bioavailability to the animal if the final dosageform is administered to the animal in the first medicament-releasestate. The release element is modifiable ex vivo to a secondmedicament-release state by an exposure to a stimulus 192A (notillustrated). In the second medicament-release state, the medicament hasa second bioavailability to the animal if the final dosage form isadministered to the animal in the second medicament-release state. Thefinal dosage form includes another dosage portion, illustrated as a “B”Portion. The another dosage portion has another chamber 3220B carryinganother medicament 190B. The another dosage portion includes anotherrelease element 3230B in another first medicament-release state. In theanother first medicament-release state, the another medicament hasanother first bioavailability to the animal if the final dosage form isadministered to the animal in the another first medicament-releasestate. The another release element is modifiable ex vivo to anothersecond medicament-release state by an exposure to another stimulus 192B(not illustrated). In the another second medicament-release state, theanother medicament has another second bioavailability to the animal ifthe final dosage form is administered to the animal in the anothersecond medicament-release state. The final dosage form includes an outerlayer 3210 enclosing the dosage portion and the another dosage portion.

In an embodiment, the first medicament-release state includes a firstmedicament-release state wherein the medicament 190A is not bioavailableto the animal 198. In an embodiment, the first medicament-release stateincludes a first medicament-release state wherein the medicament isbioavailable to the animal. In an embodiment, the secondmedicament-release state includes a second medicament-release statewherein the medicament is not bioavailable to the animal. In anembodiment, the second medicament-release state includes a secondmedicament-release state wherein the medicament is bioavailable to theanimal.

In an embodiment, the another first medicament-release state includesanother first medicament-release state wherein the another medicament190B is not bioavailable to the animal 198. In an embodiment, theanother first medicament-release state includes another firstmedicament-release state wherein the another medicament is bioavailableto the animal. In an embodiment, the another second medicament-releasestate includes another second medicament-release state wherein theanother medicament is not bioavailable to the animal. In an embodiment,the another second medicament-release state includes another secondmedicament-release state wherein the another medicament is bioavailableto the animal.

In an embodiment of the final dosage form 3202, if the firstmedicament-release state includes the medicament 190A being bioavailableto the animal and if the another first medicament-release state includesthe another medicament 190B being bioavailable to the animal 198, afirst ratio exists between the bioavailability of the medicament and thebioavailability of the another medicament. In this embodiment of thefinal dosage form, if the second medicament-release state includes themedicament 190A being bioavailable to the animal and if the anothersecond medicament-release state includes the another medicament 190Bbeing bioavailable to the animal, a second ratio exists between thebioavailability of the medicament and the bioavailability of the anothermedicament. In an embodiment, the first ratio is equal to or greaterthan the second ratio. In an embodiment, the first ratio is less thanthe second ratio.

In an embodiment of the final dosage form 3202, if the secondmedicament-release state includes the medicament 190A being bioavailableto the animal 198 and if the another second medicament-release stateincludes the another medicament 190B being bioavailable to the animal, asecond ratio exists between the bioavailability of the medicament andthe bioavailability of the another medicament.

In an embodiment, the medicament 190A and the another medicament 190Bare at least substantially similar instances of one medicament. In anembodiment, the medicament and the another medicament are at leastsubstantially different medicaments. In an embodiment, the firstbioavailability to the animal includes a first bioavailabilitycharacteristic and the second bioavailability to the animal includes asecond bioavailability characteristic.

In an embodiment, the release element 3230A is at least substantiallysimilar to the another release element 3230B. In an embodiment, therelease element is at least substantially different from the anotherrelease element.

In an embodiment, the stimulus 190A is at least substantially similar tothe another stimulus 190B. In an embodiment, the stimulus is at leastsubstantially different from the another stimulus.

In an embodiment, the final dosage form 3202 further includes anindicator element 3280A configured to indicate an exposure of therelease element 3230A to the stimulus 192A or the another stimulus 192B.In an embodiment, the final dosage form 3202 further includes anotherindicator element 3280B configured to indicate an exposure of theanother release element to the stimulus or the another stimulus. In anembodiment, the final dosage form further includes an indicator element,for example, indicator element 3280A, configured to indicate an exposureof at least one of the release element or the another release element tothe stimulus or the another stimulus.

In an embodiment, the final dosage form 3202 includes a containmentelement 3240A or a containment element 3240B configured to respectfullyretain the medicament 190A or the another medicament 190B until thefinal dosage form is administered to the animal 198.

In an embodiment, the final dosage form 3202 further includes a furtherdosage portion (not illustrated). The further dosage portion includes afurther chamber carrying a further medicament. The further dosageportion also includes a further release element in a further firstmedicament-release state. In the further first medicament-release state,the further medicament has a further first bioavailability to the animal198 if the final dosage form is administered to the animal in thefurther first medicament-release state. The further release element ismodifiable ex vivo to a further second medicament-release state by anexposure to a further stimulus. In the further second medicament-releasestate, the further medicament has a further second bioavailability tothe animal if the final dosage form is administered to the animal in thefurther second medicament-release state.

The following table illustrates several states of an example of thefinal dosage form 3202:

TABLE 2 Example bioavailability configurations Example Configuration #1Example Configuration #2 Bioavailability Profile Bioavailability ProfileState of release RE 1 RE 2 RE 1 RE2 element (RE) (100 mg) (200 mg (100mg (200 mg) TR) TR) State 1 0 0 1 0 (initial) State 2 1 0 0 0 (stimulusto RE of chamber 1) State 3 0 1 1 1 (stimulus to RE of chamber 2) State4 1 1 0 1 (stimuli to REs of chambers 1 & 2) 0 = medicament issubstantially not bioavailable 1 = medicament is bioavailable

FIG. 42 illustrates an example environment 3300. The environmentincludes a final dosage form 3302 for administering medicament to theanimal 198. The final dosage form includes a dosage portion, illustratedas “A” Portion, having a chamber 3320A carrying a medicament 190A. Thedosage portion includes a release element 3330A in amedicament-retention state. The medicament is substantially notbioavailable to the animal if the final dosage form is administered tothe animal in the first medicament-retention state. The release elementis modifiable ex vivo to a medicament-release state by an exposure to astimulus. The medicament is bioavailable to the animal if the finaldosage form is administered to the animal in the medicament-releasestate. The final dosage form includes another dosage portion,illustrated as “B” Portion, having another chamber 3320B carryinganother medicament 190B. The another dosage portion includes anotherrelease element 3330B in another medicament-retention state. The anothermedicament is substantially not bioavailable to the animal if the finaldosage form is administered to the animal in the anothermedicament-retention state. The another release element is modifiable exvivo to another medicament-release state by an exposure to anotherstimulus. The another medicament is bioavailable to the animal if thefinal dosage form is administered to the animal in the anothermedicament-release state.

FIG. 43 illustrates an example environment 3400 that includes a finaldosage form 3405 and an operational flow 3410. The final dosage formincludes a dosage portion having a chamber carrying a medicament. Thedosage portion also includes a release element in a firstmedicament-release state. The medicament has a first bioavailability tothe animal if the final dosage form is administered to the animal in thefirst medicament-release state. The release element modifiable ex vivoto a second medicament-release state by an exposure to a stimulus,wherein the medicament has a second bioavailability to the animal if thefinal dosage form is administered to the animal in the secondmedicament-release state. The final dosage form also includes anotherdosage portion having another chamber carrying another medicament. Theanother dosage portion also includes another release element in anotherfirst medicament-release state. The another medicament has another firstbioavailability to the animal if the final dosage form is administeredto the animal in the another first medicament-release state. The anotherrelease element modifiable ex vivo to another second medicament-releasestate by an exposure to another stimulus. The another medicament hasanother second bioavailability to the animal if the final dosage form isadministered to the animal in the another second medicament-releasestate. In an embodiment, the final dosage form 3405 may be substantiallysimilar to the final dosage form 3202 described in conjunction with FIG.41.

After a start operation, the operational flow 3410 includes amodification operation 3420. The modification operation includestransforming the final dosage form 3405 into a selectedmedicament-release profile by initiating an ex vivo exposure of therelease element or the another release element to a modificationstimulus respectfully selected from the stimulus and the anotherstimulus. For example, the selected medicament-release profile mayinclude a configuration of bioavailabilities of the medicament and theanother medicament to achieve a prescribed medicament dosage. Theoperational flow includes an end operation. In an embodiment, theoperational flow may be implemented using the system 2100 described inconjunction with FIG. 27.

FIG. 44 illustrates an alternative embodiment of the operational flow3410 of FIG. 43. The operational flow may include at least oneadditional operation. The at least one additional operation may includea treatment-order operation 3450, a release-state selection operation3460, or a stimulus selection operation 3470. The treatment-orderoperation includes receiving a signal indicative of a chosen medicamentbioavailability of the final dosage form 3405. In an embodiment, thetreatment-order operation may include a medicament bioavailabilityindicated by a physician's prescription, a request by a person toreceive the final dosage form, or a table. In an embodiment, thetreatment-order operation may be implemented using the system 2100described in conjunction with FIG. 21. The treatment-order operation mayinclude at least one additional operation. The at least one additionaloperation may include an operation 3452 or an operation 3454. Theoperation 3452 includes receiving a machine-initiated signal indicativeof the chosen medicament bioavailability of the final dosage form. In anembodiment, the operation 3452 may be implemented using the othercircuit(s) 2190 to receive data or an email indicative of the chosenmedicament bioavailability of the final dosage form. The operation 3454includes receiving a signal responsive to human-initiated indication ofthe chosen medicament bioavailability of the final dosage form. In anembodiment, the operation 3454 may be implemented using the userinterface 2195 to receive a human-initiated input by the person 2199.

The release-state selection operation 3460 includes selecting amedicament-release state of the release element or of the anotherrelease element in response to the chosen medicament-bioavailability ofthe final dosage form. In an embodiment, the release-state selectionoperation may be implemented using the system 2100 described inconjunction with FIG. 21. The release-state selection operation mayinclude at least one additional operation, such as an operation 3462.The operation 3462 includes electronically selecting amedicament-release state of the release element or of the anotherrelease element in response to the selected medicament-bioavailabilityof the final dosage form. The selecting a medicament-release state isbased on an electronically-stored database relating medicament-releasestate and medicament-bioavailability of the final dosage form, acomputer-implemented decision table, a digitally-maintained final dosageform transformation table, or a digital library correlatingmedicament-release state and medicament-bioavailability of the finaldosage form. In an embodiment, the operation 3462 may be implementedusing the release-state selection circuit 2165 described in conjunctionwith FIG. 21. In another embodiment, the operation 3462 may beimplemented using a combination of the release-state selection circuit2165, the computing device 2175, and/or the final dosage form andstimulus exposure database 2182 described in conjunction with FIG. 21.

The stimulus selection operation 3470 includes selecting themodification stimulus from the stimulus or the another stimulus inresponse to the selected medicament-release state. In an embodiment, thestimulus selection operation may be implemented using the system 2100described in conjunction with FIG. 21. The stimulus selection operationmay include at least one additional operation, such as an operation3472. The operation 3472 includes electronically selecting themodification stimulus from the stimulus or the another stimulus inresponse to the selected medicament-release state, the selecting thestimulus based on an electronically-stored database relating stimuli andmedicament-release state of the final dosage form, acomputer-implemented decision table, a digitally-maintained final dosageform transformation table, or a digital library correlatingmedicament-release state of the final dosage form and stimuli. In anembodiment, the operation 3472 may be implemented using the stimulusselection circuit 2170 described in conjunction with FIG. 21. In anotherembodiment, the operation 3472 may be implemented using a combination ofthe stimulus selection circuit 2170, the computing device 2175, and/orthe final dosage form and stimulus exposure database 2182 described inconjunction with FIG. 21. The modification operation 3420 is describedin conjunction with FIG. 43.

FIG. 45 illustrates an example environment 3500. The environmentincludes an article of manufacture 3501. The article of manufactureincludes a final dosage form 502 for administering medicament to ananimal. The final dosage form is described in conjunction with FIG. 5.In another embodiment, the final dosage form 502 is substantiallysimilar to the final dosage 3310 described in conjunction with FIG. 42.

The article of manufacture 3501 also includes instructions 3570specifying an ex vivo exposure of the release element 530A to thestimulus 192A (not shown) of the stimulus 192, or an ex vivo exposure ofthe another release element 530B to the another stimulus 192B (notshown) of the stimulus 190. The instructions when implemented transformthe release element to the second medicament-release state or theanother release element to the another second medicament-release state.In an embodiment, the instructions may be implemented using the system2100 described in conjunction with FIG. 27.

FIG. 46 illustrates an example article of manufacture 3602 foradministering medicament to an animal. The article of manufactureincludes a first portion 3610 and a second portion 3650. The firstportion includes means 3620 for carrying a medicament 190A. In anembodiment, the means 3620 includes means for releasably holding amedicament. The first portion also includes means 3624 for medicamentrelease control in a first state wherein the medicament has a firstbioavailability to the animal if the article of manufacture isadministered to the animal. The means for medicament release control ismodifiable ex vivo to a second state by an exposure to a stimulus,wherein the medicament has a second bioavailability to the animal if thearticle of manufacture is administered to the animal. The first portionfurther includes the medicament 190A. In an embodiment, the firstportion includes means 3628 for indicating an exposure of the means formedicament release control to the stimulus.

The second portion 3650 includes another means 3660 for carrying anothermedicament 190B. The second portion also includes another means 3664 formedicament release control in another first state wherein the anothermedicament has another first bioavailability to the animal if thearticle of manufacture is administered to the animal. The another meansfor medicament release control is modifiable ex vivo to another secondstate by an exposure to another stimulus, wherein the another medicamenthas another second bioavailability to the animal if the article ofmanufacture is administered to the animal. The second portion furtherincludes the another medicament. In an embodiment, the second portionincludes another means 3668 for indicating an exposure of the anothermeans for medicament release control to the another stimulus.

FIG. 47 illustrates an environment 3700. The environment includes afinal dosage form 3702 for administering medicament to the animal 198.The final dosage form includes a dosage portion, illustrated as “ADosage Portion.” The dosage portion includes a medicament 190A. Thedosage portion also include a release element 3730A in a firstmedicament-release state wherein the medicament has a firstbioavailability to the animal if the final dosage form is administeredto the animal in the first medicament-release state. The release elementis modifiable ex vivo to a second medicament-release state by anexposure to a stimulus, wherein the medicament has a secondbioavailability to the animal if the final dosage form is administeredto the animal in the second medicament-release state.

The final dosage form 3702 also includes another dosage portion,illustrated as “Another Dosage Portion.” The another dosage portionincludes a medicament 190B. The another dosage portion also includesanother release element 3730B in another first medicament-release statewherein the another medicament has another first bioavailability to theanimal if the final dosage form is administered to the animal in theanother first medicament-release state. The another release element ismodifiable ex vivo to another second medicament-release state by anexposure to another stimulus, wherein the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal in the another second medicament-releasestate.

In an embodiment, the first medicament-release state wherein themedicament has a first bioavailability to the animal includes a firstmedicament-release state wherein the medicament is not bioavailable tothe animal. In an embodiment, the first medicament-release state whereinthe medicament has a first bioavailability to the animal includes afirst medicament-release state wherein the medicament is bioavailable tothe animal. In an embodiment, the second medicament-release statewherein the medicament has a second bioavailability to the animalincludes a second medicament-release state wherein the medicament is notbioavailable to the animal. In an embodiment, the secondmedicament-release state wherein the medicament has a secondbioavailability to the animal includes a second medicament-release statewherein the medicament is bioavailable to the animal. In an embodiment,the first bioavailability to the animal includes a first bioavailabilitycharacteristic and the second bioavailability to the animal includes asecond bioavailability characteristic.

In an embodiment, the another first medicament-release state wherein theanother medicament has another first bioavailability to the animalincludes another first medicament-release state wherein the anothermedicament is not bioavailable to the animal. In an embodiment, theanother first medicament-release state wherein the another medicamenthas another first bioavailability to the animal includes another firstmedicament-release state wherein the another medicament is bioavailableto the animal. In an embodiment, the another second medicament-releasestate wherein the another medicament has another second bioavailabilityto the animal includes another second medicament-release state whereinthe another medicament is not bioavailable to the animal. In anembodiment, the another second medicament-release state wherein theanother medicament has another second bioavailability to the animalincludes another second medicament-release state wherein the anothermedicament is bioavailable to the animal.

In an embodiment, the stimulus includes at least one of a mechanicalstimulus, a non-ionizing radiation stimulus, an ionizing radiationstimulus, a chemical stimulus, an acoustic stimulus, an ultrasoundstimulus, a radio wave stimulus, a microwave stimulus, a light wavestimulus, or a thermal stimulus.

FIG. 47 also illustrates another embodiment of the example environment3700. The environment includes a final dosage form 3702 foradministering a medicament to the animal. The final dosage form includesa dosage portion, illustrated as “A” Dosage Portion. The dosage portionincludes a medicament 190A. The dosage portion also include a releaseelement 3730A. The release element is in a medicament-holding statewherein the medicament is substantially not bioavailable to the animalif the final dosage form is administered to the animal in themedicament-holding state. The release element is modifiable ex vivo to amedicament-discharging state by an exposure to a stimulus wherein themedicament is bioavailable to the animal if the final dosage form isadministered to the animal in the medicament-discharging state.

The final dosage form 3702 also includes another dosage portion,illustrated as “B” Dosage Portion. The another dosage portion includes amedicament 190B. The another dosage portion also includes anotherrelease element 3730B in another medicament-holding state wherein theanother medicament is substantially not bioavailable to the animal ifthe final dosage form is administered to the animal in the anothermedicament-holding state. The another release element is modifiable exvivo to another medicament-discharge state by an exposure to anotherstimulus wherein the another medicament is bioavailable to the animal ifthe final dosage form is administered to the animal in the anothermedicament-discharge state. In an embodiment, the final dosage form 3702further includes an outer layer 3710 carrying the dosage portion and theanother dosage portion.

The following table illustrates several states of example embodiments ofthe final dosage form 2610:

TABLE 3 Example bioavailability configurations Example Configuration #1Example Configuration #2 Bioavailability Profile Bioavailability ProfileState of RE 1 RE 2 RE 1 RE 2 release (100 mg) (200 mg TR) (100 mg (200mg element Medicament medicament (RE) A) B) State 1 0 0 0 0 (initial)State 2 1 0 1 0 (stimulus to first RE) State 3 0 1 0 1 (stimulus tosecond RE) State 4 1 1 1 1 (stimuli to both REs) 0 = medicament issubstantially not bioavailable 1 = medicament is bioavailable

FIG. 48 illustrates an example environment 3800. The example environmentincludes a final dosage form 3810 for administering medicament to ananimal. The final dosage form includes a dosage portion 3804A, and isillustrated in an embodiment as including two molecules. In anotherembodiment, the dosage portion may include a large number of molecules.A molecule of the dosage portion includes a release element; themolecule is generally illustrated as including a release element 3802having a medicament (not shown). In an embodiment, a small moleculeincludes the release element. In an embodiment, a particle or polymermaterial includes the release element. In an embodiment, an intelligentmolecule includes the release element. In an embodiment, a gel,illustrated as a hydrogel 3802A, includes the release element having anassociated medicament 190A. In an embodiment, a liposome, illustrated asa liposome 3802B, includes the release element having an associatedmedicament 190B. In an embodiment, a nanoparticle includes the releaseelement, illustrated as a nanosphere 3802C having an associatedmedicament 190C.

The release element 3802 is in a first medicament-release state whereinthe medicament has a first bioavailability to the animal 198 if thefinal dosage form is administered to the animal in the firstmedicament-release state. The release element is modifiable ex vivo to asecond medicament-release state by an exposure to a stimulus, whereinthe medicament has a second bioavailability to the animal if the finaldosage form is administered to the animal in the secondmedicament-release state.

The final dosage form also includes another dosage portion, illustratedas a dosage portion 3804B, illustrated in an embodiment as including twomolecules. In another embodiment, the another dosage portion may includea large number of molecules. A molecule of the another dosage portionincludes another release element, generally also illustrated as releaseelement 3802 having another medicament (not shown). In an embodiment,another small molecule includes the another release element. In anembodiment, another particle or polymer material includes the anotherrelease element. In an embodiment, another intelligent molecule includesthe another release element. In an embodiment, another gel, illustratedas the hydrogel 3802A, includes the another release element having anassociated medicament 190A. In an embodiment, another liposome,illustrated as the liposome 3802B, includes the another release elementhaving an associated medicament 190B. In an embodiment, anothernanoparticle, illustrated as the nanosphere 3802C, includes the anotherrelease element having an associated medicament 190C.

The another release element is in another first medicament-release statewherein the another medicament has another first bioavailability to theanimal if the final dosage form is administered to the animal in theanother first medicament-release state. The another release element ismodifiable ex vivo to another second medicament-release state by anexposure to another stimulus, wherein the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal in the another second medicament-releasestate.

While FIG. 48 illustrates the molecules comprising release elementsdosage portion 3804A in a proximity, in an embodiment, the moleculescomprising release elements dosage portion 3804A may be distributed inany manner throughout the final dosage form 3810. Likewise, in anembodiment, the molecules comprising release elements dosage portion3804B may be distributed in any manner throughout the final dosage form3810. Further, the molecules comprising release elements dosage portion3804A and the molecules comprising release elements dosage portion 3804Bmay be intermingled in any manner throughout the final dosage form 3810.In an embodiment, the molecules that comprise the dosage portion 3804Aand 3804B may be substantially a same type of molecule, or may besubstantially different types of molecules.

FIG. 48 also illustrates another embodiment of the example environment3800. The another embodiment of the example environment includes a finaldosage form 3810 for administering medicament to an animal. The finaldosage form includes a dosage portion 3804A, illustrated in anembodiment as including two molecules. A molecule of the dosage portionincludes a release element, generally illustrated as release element3802, having a medicament (not shown). In an embodiment, a smallmolecule includes the release element. In an embodiment, a particle orpolymer material includes the release element. In an embodiment, anintelligent molecule includes the release element. In an embodiment, agel, illustrated as a hydrogel 3802A, includes the release elementhaving a medicament 190A. In an embodiment, a liposome, illustrated as aliposome 3802B, includes the release element having a medicament 190B.In an embodiment, a nanoparticle includes the release element,illustrated as a nanosphere 2202C having a medicament 190C.

The release element 3802 is in a medicament-holding state wherein themedicament is substantially not bioavailable to the animal 198 if thefinal dosage form 3810 is administered to the animal in themedicament-holding state. The release element is modifiable ex vivo to amedicament-discharging state by an exposure to a stimulus wherein themedicament is bioavailable to the animal if the final dosage form isadministered to the animal in the medicament-discharging state.

The final dosage form also includes another dosage portion 3804B,illustrated in an embodiment, as including two molecules. A molecule ofthe another dosage portion includes another release element, generallyalso illustrated as release element 3802 having another medicament (notshown). In an embodiment, another small molecule includes the anotherrelease element. In an embodiment, another particle or polymer materialincludes the another release element. In an embodiment, anotherintelligent molecule includes the another release element. In anembodiment, another gel, illustrated as the hydrogel 3802A, includes theanother release element having a medicament 190A. In an embodiment,another liposome, illustrated as the liposome 3802B, includes theanother release element having a medicament 190B. In an embodiment,another nanoparticle, illustrated as the nanosphere 3802C, includes theanother release element having a medicament 190C.

The another release element is in another medicament-holding statewherein the another medicament is substantially not bioavailable to theanimal 198 if the final dosage form 3810 is administered to the animalin the another medicament-holding state. The another release element ismodifiable ex vivo to another medicament-discharge state by an exposureto another stimulus wherein the another medicament is bioavailable tothe animal if the final dosage form is administered to the animal in theanother medicament-discharge state.

FIG. 49 illustrates an example environment 3900 that includes a finaldosage form 3905 and an operational flow 3910. The final dosage formincludes a dosage portion having a medicament. The dosage portionincludes a release element in a first medicament-release state whereinthe medicament has a first bioavailability to the animal if the finaldosage form is administered to the animal in the firstmedicament-release state. The release element is modifiable ex vivo to asecond medicament-release state by an exposure to a stimulus, whereinthe medicament has a second bioavailability to the animal if the finaldosage form is administered to the animal in the secondmedicament-release state. The final dosage form also includes anotherdosage portion having another medicament. The another dosage portionincludes another release element in another first medicament-releasestate wherein the another medicament has another first bioavailabilityto the animal if the final dosage form is administered to the animal inthe another first medicament-release state. The another release elementis modifiable ex vivo to another second medicament-release state by anexposure to another stimulus, wherein the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal in the another second medicament-releasestate. In an embodiment, the final dosage form 3905 is substantiallysimilar to the final dosage form 3702 described in conjunction with FIG.47, or the final dosage form 3810 described in conjunction with FIG. 48.

After a start operation, the operational flow 3910 includes acustomization operation 3920. The customization operation includestransforming the final dosage form 3905 into a selected medicamentrelease profile by initiating an ex vivo exposure of the release elementor the another release element to a modification stimulus respectfullyselected from the stimulus or the another stimulus. The operational flowincludes an end operation. In an embodiment, the customization operationmay include at least one additional operation, such as the operation3922. The operation 3922 includes transforming the final dosage forminto a selected medicament release profile by initiating an ex vivoexposure of the release element and the another release element to thestimulus and the another stimulus. In an embodiment, the operationalflow 3910 may be implemented using the system 2100 described inconjunction with FIG. 27.

FIG. 50 illustrates an example alternative embodiment of the operationalflow 3910 of FIG. 49. The operational flow may include at least oneadditional operation. The at least one additional operation may includea treatment-order operation 3950, a release-state selection operation3960, or a stimulus selection operation 3970. The treatment-orderoperation includes receiving a signal indicative of a chosen medicamentbioavailability of the final dosage form 3905. In an embodiment, thetreatment-order operation may be implemented using the system 2100described in conjunction with FIG. 21. The treatment-order operation mayinclude at least one additional operation. The at least one additionaloperation may include an operation 3952 or an operation 3954. Theoperation 3952 includes receiving a machine-initiated signal indicativeof the chosen medicament bioavailability of the final dosage form. In anembodiment, the operation 3952 may be implemented using the othercircuit(s) 2190 to receive data or an email indicative of the chosenmedicament bioavailability of the final dosage form. The operation 3954includes receiving a signal responsive to human-initiated indication ofthe chosen medicament bioavailability of the final dosage form. In anembodiment, the operation 3954 may be implemented using the userinterface 2195 to receive a human-initiated input by the person 2199described in conjunction with FIG. 27.

The release-state selection operation 3960 includes selecting amedicament-release state of the release element or of the anotherrelease element in response to the chosen medicament-bioavailability ofthe final dosage form. In an embodiment, the release-state selectionoperation may be implemented using the system 2100 described inconjunction with FIG. 21. The release-state selection operation mayinclude at least one additional operation, such as an operation 3962.The operation 3962 includes electronically selecting amedicament-release state of the release element or of the anotherrelease element in response to the selected medicament-bioavailabilityof the final dosage form. The selecting a medicament-release state isbased on an electronically-stored database relating medicament-releasestate and medicament-bioavailability of the final dosage form, acomputer-implemented decision table, a digitally-maintained final dosageform transformation table, or a digital library correlatingmedicament-release state and medicament-bioavailability of the finaldosage form. In an embodiment, the operation 3962 may be implementedusing the release-state selection circuit 2165 described in conjunctionwith FIG. 21. In another embodiment, the operation 3962 may beimplemented using a combination of the release-state selection circuit2165, the computing device 2175, and/or the final dosage form andstimulus exposure database 2182 described in conjunction with FIG. 21.

The stimulus selection operation 3970 includes selecting themodification stimulus from the stimulus or the another stimulus inresponse to the selected medicament-release state. In an embodiment, thestimulus selection operation may be implemented using the system 2100described in conjunction with FIG. 21. The stimulus selection operationmay include at least one additional operation, such as an operation3972. The operation 3972 includes electronically selecting themodification stimulus from the stimulus or the another stimulus inresponse to the selected medicament-release state, the selecting thestimulus based on an electronically-stored database relating stimuli andmedicament-release state of the final dosage form, acomputer-implemented decision table, a digitally-maintained final dosageform transformation table, or a digital library correlatingmedicament-release state of the final dosage form and stimuli. In anembodiment, the operation 3972 may be implemented using the stimulusselection circuit 2170 described in conjunction with FIG. 21. In anotherembodiment, the operation 3972 may be implemented using a combination ofthe stimulus selection circuit 2170, the computing device 2175, and/orthe final dosage form and stimulus exposure database 2182 described inconjunction with FIG. 21. The modification operation 3920 is describedin conjunction with FIG. 49.

FIG. 51 illustrates an example environment 4000 that includes an articleof manufacture 4001. In an embodiment, the article of manufactureincludes the final dosage form 3702 described in conjunction with FIG.47. The article of manufacture also includes instructions 4070. Theinstructions specify an ex vivo exposure of the release element of thefinal dosage form to the stimulus or an ex vivo exposure of the anotherrelease element of the final dosage form to the another stimulus. Theinstructions when implemented transform the release element to thesecond medicament-release state or the another release element to theanother second medicament-release state.

FIG. 52 illustrates an example environment 4100 that includes an articleof manufacture 4101. In an embodiment, the article of manufactureincludes the final dosage form 3810 described in conjunction with FIG.48. The article of manufacture also includes instructions 4170. Theinstructions specify an ex vivo exposure of the release element of thefinal dosage form to the stimulus or an ex vivo exposure of the anotherrelease element of the final dosage form to the another stimulus. Theinstructions when implemented transform the release element to thesecond medicament-release state or the another release element to theanother second medicament-release state.

FIG. 53 illustrates an example article of manufacture 4202 foradministering medicament to an animal. The article includes themedicament 190A. The article also includes means 4224 for medicamentrelease control in a first state wherein the medicament has a firstbioavailability to the animal if the article of manufacture isadministered to the animal. The means for medicament release control ismodifiable ex vivo to a second state by an exposure to a stimulus,wherein the medicament has a second bioavailability to the animal if thearticle of manufacture is administered to the animal. The articleincludes another medicament 190B. The article also includes anothermeans 4264 for medicament release control in another first state whereinthe another medicament has another first bioavailability to the animalif the article of manufacture is administered to the animal. The anothermeans for medicament release control is modifiable ex vivo to anothersecond state by an exposure to another stimulus, wherein the anothermedicament has another second bioavailability to the animal if thearticle of manufacture is administered to the animal.

In an embodiment, the article 4202 includes means 4228 for indicating anexposure of the means 4224 for medicament release control to thestimulus 190A. In an embodiment, the article includes another means 4268for indicating an exposure of the another means 4264 for medicamentrelease control to the another stimulus 190B. In an embodiment, thearticle includes means 4280 for protecting the article of manufactureagainst an ex vivo environment. In an embodiment, the article includesmeans 4290 for carrying the article of manufacture into the animal.

FIG. 54 illustrates an example environment 4300. The environmentincludes a final dosage form 4310 for administering medicament to theanimal 198. The final dosage form includes a dosage portion having asite and a medicament in a first association. The dosage portion isillustrated as “A Dosage Portion,” and illustrates a molecule having asite and the medicament (illustrated below as medicaments 190A, 190B,and 190C) in a first association. In another embodiment, the “A DosagePortion” may include a large number of molecules each respectfullyhaving a site and an instance of the medicament in a first association.In an embodiment, the site is provided by a gel, illustrated as ahydrogel 4302A, and the medicament 190A is in a first association withthe site. In an embodiment, the site of the dosage portion is providedby a liposome, illustrated as a liposome 4302B, and the medicament 190Bis in a first association with the site. In an embodiment, the site ofthe dosage portion is provided by a nanoparticle, illustrated asnanosphere 4302C and the medicament 190C is in a first association withthe site. In an embodiment, the site of the dosage portion includes anactive site of a molecule. In an embodiment, the site of the dosageportion includes a binding site of a molecule. In an embodiment, thesite of the dosage portion includes a site of an intelligent molecule.

In the first association, the medicament has a first bioavailability tothe animal if the final dosage form is administered to the animal. Thefirst association of the site and the medicament is modifiable ex vivoto a second association of the site and the medicament by an exposure toa stimulus, wherein the medicament has a second bioavailability to theanimal if the final dosage form is administered to the animal.

The final dosage form 4310 includes another dosage portion havinganother site and another medicament in another first association. Theanother dosage portion is illustrated as “Another Dosage Portion,” andillustrates another molecule having another site and the anothermedicament (illustrated below as medicaments 190A, 190B, and 190C) inanother first association. In another embodiment, the “Another DosagePortion” may include a large number of another molecules eachrespectfully having another site and an instance of the medicament inanother first association. In an embodiment, the another site isprovided by a gel, illustrated as a hydrogel 4302A, and the medicament190A is in a first association with the another site. In an embodiment,the another site of the another dosage portion is provided by aliposome, illustrated as a liposome 4302B, and the medicament 190B is inanother first association with the another site. In an embodiment, theanother site of the another dosage portion is provided by ananoparticle, illustrated as nanosphere 4302C and the medicament 190C isin another first association with the another site. In an embodiment,the another site of the another dosage portion includes an active siteof another molecule. In an embodiment, the another site of the anotherdosage portion includes another binding site of another molecule. In anembodiment, the another site of the another dosage portion includesanother site of another intelligent molecule.

In the another first association, the another medicament has anotherfirst bioavailability to the animal if the final dosage form isadministered to the animal. The another first association of the anothersite and the another medicament is modifiable ex vivo to another secondassociation of the another site and the another medicament by anexposure to another stimulus, wherein the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal.

In an embodiment, the dosage portion and the another dosage portion maybe in an unstructured proximity. For example, the dosage portion and theanother dosage portion may be dispersed or suspended in a solidtransport medium, a liquid transport medium, a gel transport medium, ora solid transport medium. In another embodiment, the dosage portion andthe another dosage portion may be in a structured relationship in asolid transport medium, a liquid transport medium, a gel transportmedium, or a solid transport medium.

In an embodiment, the dosage portion includes a particle. In anembodiment, the dosage portion includes a polymeric material. In anembodiment, the another dosage portion includes another particle. In anembodiment, the site and the medicament in a first association includesa site of a particle or polymeric material in a first association withthe medicament. In an embodiment, the site and the medicament in a firstassociation includes a site of a particle or polymeric materialencapsulating the medicament and in a first association with themedicament. In an embodiment, the site and the medicament in a firstassociation includes a particle or polymeric material site that at leastone of engages, retains, or binds the medicament in a first association.In an embodiment, the another dosage portion includes another polymericmaterial.

In an embodiment, the first bioavailability to the animal 198 includesthe medicament is not bioavailable to the animal. In an embodiment, thefirst bioavailability to the animal includes the medicament isbioavailable to the animal. In an embodiment, the second bioavailabilityto the animal includes the medicament is not bioavailable to the animal.In an embodiment, the second bioavailability to the animal includes themedicament is bioavailable to the animal. In an embodiment, the anotherfirst bioavailability to the animal includes the another medicament isnot bioavailable to the animal. In an embodiment, the another firstbioavailability to the animal includes the another medicament isbioavailable to the animal. In an embodiment, the another secondbioavailability to the animal includes the another medicament is notbioavailable to the animal. In an embodiment, the another secondbioavailability to the animal includes the another second medicament isbioavailable to the animal.

In an embodiment, the first bioavailability to the animal includes afirst bioavailability characteristic and the second bioavailability tothe animal includes a second bioavailability characteristic. In anembodiment, the another first bioavailability to the animal includesanother first bioavailability characteristic and the another secondbioavailability to the animal includes another second bioavailabilitycharacteristic.

In an embodiment, the stimulus includes at least one of a mechanicalstimulus, a non-ionizing radiation stimulus, an ionizing radiationstimulus, a chemical stimulus, an acoustic stimulus, an ultrasoundstimulus, a radio wave stimulus, a microwave stimulus, a light wavestimulus, or a thermal stimulus. In an embodiment, the another stimulusincludes at least one of a mechanical stimulus, a non-ionizing radiationstimulus, an ionizing radiation stimulus, a chemical stimulus, anacoustic stimulus, an ultrasound stimulus, a radio wave stimulus, amicrowave stimulus, a light wave stimulus, or a thermal stimulus.

FIG. 54 illustrates another embodiment of the final dosage form 4130 foradministering medicament to the animal 198. In this another embodiment,in the first association of site and the medicament, the medicament issubstantially not bioavailable to the animal 198 if the final dosageform 4130 is administered to the animal. The first association of thesite and the medicament is modifiable ex vivo to a second association byan exposure to a stimulus of the stimulus 192, wherein the medicament issubstantially bioavailable to the animal if the final dosage form isadministered to the animal.

In this another embodiment, in the another first association of theanother site and the another medicament, the another medicament issubstantially not bioavailable to the animal 198 if the final dosageform 4130 is administered to the animal. The another first associationof the another site and the another medicament is modifiable ex vivo toanother second association by an exposure to another stimulus, whereinthe another medicament is substantially bioavailable to the animal ifthe final dosage form is administered to the animal.

FIG. 55 illustrates an example environment 4400 that includes a finaldosage form 4405 and an operational flow 4420. The final dosage form4405 is substantially similar to the final dosage form 4310 described inconjunction with FIG. 54.

After a start operation, the operational flow includes a customizationoperation 4420. The customization operation includes transforming thefinal dosage form into a selected medicament release state by initiatingan ex vivo exposure of the first association of the site and themedicament or the another first association of the another site and theanother medicament to a modification stimulus respectfully selected fromthe stimulus or the another stimulus. The operational flow includes anend operation.

In an embodiment, the customization operation 4420 may include at leastone additional operation, such as an operation 4422. The operation 4422includes transforming the final dosage form into a selected medicamentrelease state by initiating an ex vivo exposure of the first associationof the site and the medicament and the another first association of theanother site and the another medicament to the stimulus and the anotherstimulus. In an embodiment, the operational flow 4420 may be implementedusing the system 2100 described in conjunction with FIG. 27.

FIG. 56 illustrates an alternative embodiment of the operational flow4420 described in FIG. 55. In an embodiment, the operational flow mayinclude at least one additional operation. The at least one additionaloperation may include a treatment-order operation 4450, a release-stateselection operation 4460, or a modification-stimulus selection operation4470. The treatment-order operation includes receiving a signalindicative of a chosen medicament bioavailability of the final dosageform 4405. The treatment-order operation may be implemented using thesystem 2100 described in conjunction with FIG. 27. In an embodiment, thetreatment-order operation may include at least one additional operation.The at least one additional operation may include an operation 4452 oran operation 4454. The operation 4452 includes receiving amachine-initiated signal indicative of the chosen medicamentbioavailability of the final dosage form. In an embodiment, theoperation 4452 may be implemented using the other circuit(s) 2190 toreceive data, an email or fax indicative of the chosen medicamentbioavailability of the final dosage form. The operation 4454 includesreceiving a signal responsive to human-initiated indication of thechosen medicament bioavailability of the final dosage form. In anembodiment, the operation 4454 may be implemented using the userinterface 2195 of FIG. 27 to receive a human-initiated input by theperson 2199.

The release-state selection operation 4460 includes selecting amedicament-release state of the site and the medicament or of theanother site and the another medicament in response to the chosenmedicament-bioavailability of the final dosage form. In an embodiment,the release-state selection operation may be implemented using therelease-state selection circuit 2165 of FIG. 27. In an embodiment, therelease-state selection operation may be implemented using therelease-state selection circuit 2165 and a human 2199 initiated inputentered into the user interface 2195. The release-state selectionoperation may include at least one additional operation, such as anoperation 4462. The operation 4462 includes electronically selecting amedicament-release state of the site and the medicament or of theanother site and the another medicament in response to the chosenmedicament-bioavailability of the final dosage form, the selecting amedicament-release state based on an electronically-stored databaserelating medicament-release state and medicament-bioavailability of thefinal dosage form, a computer-implemented decision table, adigitally-maintained final dosage form transformation table, or adigital library correlating medicament-release state andmedicament-bioavailability of the final dosage form. In an embodiment,the operation 4462 may be implemented using the release-state selectioncircuit 2165. In an embodiment, the operation 4462 may be implementedusing the release-state selection circuit, the computing device 2175,and/or the final dosage form and stimulus exposure database 2182 (savedon the computer-readable storage medium 2180).

The modification-stimulus selection operation 4470 includes selectingthe modification-stimulus from the stimulus or the another stimulus inresponse to the selected medicament-release state. In an embodiment,modification-stimulus selection operation may be implemented using thestimulus selection circuit 2170 described in conjunction with FIG. 27.The modification-stimulus selection operation may include at least oneadditional operation, such as the operation 4472. The operation 4472electronically selecting the modification-stimulus from the stimulus orthe another stimulus in response to the selected medicament-releasestate, the selecting the modification-stimulus based on anelectronically-stored database relating stimuli and medicament-releasestate of the final dosage form, a computer-implemented decision table, adigitally-maintained final dosage form transformation table, or adigital library correlating medicament-release state of the final dosageform and stimuli. In an embodiment, the stimulus selection circuit, thecomputing device 2175, and/or the final dosage form and stimulusexposure database 2182 may cooperatively implement the operation 4472.

FIG. 57 illustrates an example environment 4500. The environmentincludes an article of manufacture 4501. In an embodiment, the articleof manufacture includes the final dosage form 4310 described inconjunction with FIG. 54. The article of manufacture includesinstructions 4570 specifying an ex vivo exposure of the firstassociation of the site and the medicament to the stimulus or an ex vivoexposure of the another first association of the another site and theanother medicament to the another stimulus. The ex vivo exposure ifimplemented transforms the first association of the site and themedicament to the second association or the another first association ofthe another site and the another medicament to the another secondassociation.

FIG. 58 illustrates an example article of manufacture 4602 foradministering medicament to an animal. The article includes means 4624for encapsulating a medicament 190A in a first medicament-release state.In the first medicament-release state, medicament has a firstbioavailability to the animal if the article of manufacture isadministered to the animal in the first medicament-release state. Themeans for encapsulating a medicament in a first medicament-release stateis modifiable ex vivo to a second medicament-release state by anexposure to a stimulus, wherein the medicament has a secondbioavailability to the animal if the article of manufacture isadministered to the animal in the second medicament-release state. Thearticle of manufacture also includes the medicament 190A.

The article of manufacture 4602 includes another means 4664 forencapsulating another medicament 190B in another firstmedicament-release state. In the another first medicament-release state,the another medicament has another first bioavailability to the animalif the article of manufacture is administered to the animal in theanother first medicament-release state. The another means forencapsulating another medicament is modifiable ex vivo to another secondmedicament-release state by an exposure to another stimulus, wherein theanother medicament has another second bioavailability to the animal ifthe article of manufacture is administered to the animal in the anothersecond medicament-release state. The article of manufacture alsoincludes the medicament 190B.

In an embodiment, the article of manufacture may include means 4628 forindicating an exposure of the means for encapsulating a medicament in afirst medicament-release state to the stimulus. In an embodiment, thearticle of manufacture may include another means 4668 for indicating anexposure of the another means for encapsulating another medicament inanother first medicament-release state to the another stimulus. In anembodiment, the article of manufacture may include means 4680 forprotecting the article of manufacture against an ex vivo environment. Inan embodiment, the article of manufacture may include means 4590 forcarrying the article of manufacture into the animal.

FIG. 59 illustrates an example environment 4700. The environmentincludes a final dosage form 4710 for administering medicament to theanimal 198. The final dosage form includes a dosage portion, illustratedas “A Dosage Portion,” that includes a substance associated with amedicament (illustrated and described below as medicaments 190A, 190B,and 190C) in a first release-control state. In an embodiment, the “ADosage Portion” may include a large number of substances eachrespectfully associated with an instance of the medicament in a firstrelease-control state.

In an embodiment, the substance includes a gel, illustrated as ahydrogel 4702A, associated with the medicament 190A in a firstrelease-control state. In an embodiment, the substance includes aliposome, illustrated as a liposome 4702B, associated with themedicament 190B in a first release-control state. In an embodiment, thesubstance includes a nanoparticle, illustrated as nanosphere 4702Cassociated with the medicament 190C in a first release-control state. Inan embodiment, the substance includes an active site of a moleculeassociated with the medicament in a first release-control state. In anembodiment, the substance includes a molecule associated with themedicament in a first release-control state. In an embodiment, thesubstance includes an intelligent molecule associated with themedicament in a first release-control state.

In the first release control state, the medicament has a firstbioavailability to the animal 198 if the final dosage form 4710 isadministered to the animal. The substance associated with the medicamentin a first release-control state is modifiable ex vivo by an exposure toa stimulus to associate with the medicament in a second release-controlstate. In the second release-control state, the medicament has a secondbioavailability to the animal if the final dosage form is administeredto the animal.

The final dosage form 4710 includes another dosage portion, illustratedas “Another Dosage Portion,” that includes another substance associatedwith another medicament (illustrated and described as medicaments 190A,190B, and 190C) in another first release-control state. In anembodiment, the “Another Dosage Portion” may include a large number ofanother substances each respectfully associated with an instance of theanother medicament in another first release-control state.

In an embodiment, the another substance includes another gel,illustrated as a hydrogel 4702A, associated with the another medicament190A in another first release-control state. In an embodiment, theanother substance includes another liposome, illustrated as a liposome4702B, associated with the another medicament 190B in another firstrelease-control state. In an embodiment, the another substance includesanother nanoparticle, illustrated as nanosphere 4702C associated withthe another medicament 190C in another first release-control state. Inan embodiment, the another substance includes an active site of anothermolecule associated with the another medicament in another firstrelease-control state. In an embodiment, the another substance includesanother molecule associated with the medicament in a firstrelease-control state. In an embodiment, the another substance includesanother intelligent molecule associated with the another medicament inanother first release-control state.

In the another first release control state, the another medicament hasanother first bioavailability to the animal 198 if the final dosage form4710 is administered to the animal. The another substance associatedwith the another medicament in a first release-control state ismodifiable ex vivo by an exposure to another stimulus to associate withthe another medicament in another second release-control state. In thesecond release-control state, the another medicament has another secondbioavailability to the animal if the final dosage form is administeredto the animal.

In an embodiment, the dosage portion and the another dosage portion maybe in an unstructured proximity, and not necessarily physically distinctstructures. For example, the dosage portion and the another dosageportion may be dispersed or suspended in a solid transport medium, aliquid transport medium, a gel transport medium, or a solid transportmedium. In another embodiment, the dosage portion and the another dosageportion may be in a structured relationship in a solid transport medium,a liquid transport medium, a gel transport medium, or a solid transportmedium.

In an embodiment, the substance associated with the medicament in afirst release-control state includes a particle associated with themedicament in a first release-control state. In an embodiment, thesubstance associated with the medicament in a first release-controlstate includes a polymeric material associated with the medicament in afirst release-control state. In an embodiment, the substance associatedwith the medicament in a first release-control state includes a smallmolecule associated with the medicament in a first release-controlstate. In an embodiment, the substance associated with the medicament ina first release-control state includes an intelligent moleculeassociated with the medicament in a first release-control state. In anembodiment, the substance associated with the medicament in a firstrelease-control state includes an encapsulating substance associatedwith the medicament in a first release-control state. In an embodiment,the substance associated with the medicament in a first release-controlstate includes a conjugating substance joined with the medicament in afirst release-control state. In an embodiment, the substance associatedwith the medicament in a first release-control state includes a bindingsubstance bound with the medicament in a first release-control state. Inan embodiment, the substance associated with the medicament in a firstrelease-control state includes a substance at least one of engaging, orretaining the medicament in a first release-control state.

In an embodiment, the first bioavailability includes a firstbioavailability characteristic and the second bioavailability includes asecond bioavailability characteristic. In an embodiment, the firstbioavailability to the animal includes the medicament beingsubstantially not bioavailable to the animal. In an embodiment, thefirst bioavailability to the animal includes the medicament beingsubstantially bioavailable to the animal. In an embodiment, the secondbioavailability to the animal includes the medicament beingsubstantially not bioavailable to the animal. In an embodiment, thesecond bioavailability to the animal includes the medicament beingsubstantially bioavailable to the animal. In an embodiment, the secondbioavailability to the animal includes the medicament beingsubstantially bioavailable to the animal, wherein the secondbioavailability to the animal is substantially different than the firstbioavailability to the animal.

FIG. 59 also illustrates an alternative embodiment of the exampleenvironment 4700. The alternative embodiment of environment includes analternative embodiment of the final dosage form 4710 for administeringmedicament to the animal 198. The final dosage form includes a dosageportion, illustrated as “A Dosage Portion,” that includes a substanceassociated with a medicament (illustrated and described below asmedicaments 190A, 190B, and 190C) in a first state. In an embodiment,the “A Dosage Portion” may include a large number of substances eachrespectfully associated with an instance of the medicament in a firststate.

In an embodiment, the substance includes a gel, illustrated as ahydrogel 4702A, associated with the medicament 190A in a first state. Inan embodiment, the substance includes a liposome, illustrated as aliposome 4702B, associated with the medicament 190B in a first state. Inan embodiment, the substance includes a nanoparticle, illustrated asnanosphere 4702C associated with the medicament 190C in a first state.In an embodiment, the substance includes an active site of a moleculeassociated with the medicament in a first state. In an embodiment, thesubstance includes a molecule associated with the medicament in a firststate. In an embodiment, the substance includes an intelligent moleculeassociated with the medicament in a first state.

In the first state, the medicament has a first bioavailability to theanimal 198 if the final dosage form 4710 is administered to the animal.The substance associated with the medicament in a first state ismodifiable ex vivo by an exposure to a stimulus to associate with themedicament in a second state. In the second state, the medicament has asecond bioavailability to the animal if the final dosage form isadministered to the animal.

The final dosage form 4710 includes another dosage portion, illustratedas “Another Dosage Portion,” that includes another substance associatedwith another medicament (illustrated and described as medicaments 190A,190B, and 190C) in another first state. In an embodiment, the “AnotherDosage Portion” may include a large number of another substances eachrespectfully associated with an instance of the another medicament inanother first state.

In an embodiment, the another substance includes another gel,illustrated as a hydrogel 4702A, associated with the another medicament190A in another first state. In an embodiment, the another substanceincludes another liposome, illustrated as a liposome 4702B, associatedwith the another medicament 190B in another first state. In anembodiment, the another substance includes another nanoparticle,illustrated as nanosphere 4702C associated with the another medicament190C in another first state. In an embodiment, the another substanceincludes an active site of another molecule associated with the anothermedicament in another first state. In an embodiment, the anothersubstance includes another molecule associated with the medicament in afirst state. In an embodiment, the another substance includes anotherintelligent molecule associated with the another medicament in anotherfirst state.

In the another first state, the another medicament has another firstbioavailability to the animal 198 if the final dosage form 4710 isadministered to the animal. The another substance associated with theanother medicament in a first state is modifiable ex vivo by an exposureto another stimulus to associate with the another medicament in anothersecond state. In the second state, the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal.

FIG. 60 illustrates an example environment 4800 that includes a finaldosage form 4805 for administering medicament to an animal and anoperational flow 4820. The final dosage form includes a medicament. Thefinal dosage form also includes a substance associated with themedicament in a first release-control state. In the firstrelease-control state, the medicament has a first bioavailability to theanimal if the final dosage form is administered to the animal. Thesubstance is modifiable ex vivo by an exposure to a stimulus toassociate with the medicament in a second release-control state. In thesecond release-control state, the medicament has a secondbioavailability to the animal if the final dosage form is administeredto the animal. The final dosage form also includes another medicament.The final dosage form includes another substance associated with theanother medicament in another first release-control state. In theanother first release-control state, the another medicament has anotherfirst bioavailability to the animal if the final dosage form isadministered to the animal. The another substance is modifiable ex vivoby an exposure to another stimulus to associate with the anothermedicament in another second release-control state, wherein the anothermedicament has another second bioavailability to the animal if the finaldosage form is administered to the animal. In an embodiment, the finaldosage form 4805 is substantially similar to the final dosage form 4710previously described in conjunction with FIG. 59.

After a start operation, the operational flow 4810 includes acustomization operation 4820. The customization operation includestransforming the final dosage form 4805 into a selected medicamentrelease state by initiating an ex vivo exposure of the substanceassociated with the medicament in a first release-control state or an exvivo exposure of the another substance associated with the anothermedicament in another first release-control state to a modificationstimulus respectfully selected from the stimulus or the anotherstimulus. The operational flow includes an end operation. In anembodiment, the operational flow 4810 may be implemented using thesystem 2100 described in conjunction with FIG. 27.

In an alternative embodiment, the operational flow 4810 may include atleast one additional operation, such as an operation 4822. The operation4822 includes transforming the final dosage form into a selectedmedicament release state by initiating an ex vivo exposure of thesubstance associated with the medicament in a first release-controlstate and an ex vivo exposure of the another substance associated withthe another medicament in another first release-control state to thestimulus and the another stimulus.

FIG. 61 illustrates an alternative embodiment of the operational flow4805 described in conjunction with FIG. 60. In an embodiment, theoperational flow may include at least one additional operation. The atleast one additional operation may include a treatment-order operation4850, a release-state selection operation 4860, or amodification-stimulus selection operation 4870. The treatment-orderoperation includes receiving a signal indicative of a chosen medicamentbioavailability of the final dosage form. The treatment-order operationmay be implemented using the system 2100 described in conjunction withFIG. 27. The treatment-order operation may include at least oneadditional operation. The at least one additional operation may includean operation 4852 or an operation 4854. The operation 4852 includesreceiving a machine-initiated signal indicative of a chosen medicamentbioavailability of the final dosage form. In an embodiment, theoperation 4852 may be implemented using the other circuit(s) 2190 toreceive data, an email or fax indicative of the chosen medicamentbioavailability of the final dosage form. The operation 4854 includesreceiving a human-initiated a signal indicative of a chosen medicamentbioavailability of the final dosage form. In an embodiment, theoperation 4854 may be implemented using the user interface 2195 of FIG.27 to receive a human-initiated input by the person 2199.

The release-state selection operation 4860 includes selecting themedicament-release state of the substance associated with the medicamentor of the another substance associated with the another medicament inresponse to the chosen medicament-bioavailability of the final dosageform. In an embodiment, the release-state selection operation may beimplemented using the release-state selection circuit 2165 of FIG. 27.In an embodiment, the release-state selection operation may beimplemented using the release-state selection circuit 2165 and a human2199 initiated input entered into the user interface 2195. In anembodiment, the release-state selection operation may include at leastone additional operation, such as an operation 4862. The operation 4862includes electronically selecting the medicament-release state of thesubstance associated with the medicament or of the another substanceassociated with the another medicament in response to the chosenmedicament-bioavailability of the final dosage form. The selecting amedicament-release state is based on an electronically-stored databaserelating medicament-release state and medicament-bioavailability of thefinal dosage form, a computer-implemented decision table, adigitally-maintained final dosage form transformation table, or adigital library correlating medicament-release state andmedicament-bioavailability of the final dosage form. In an embodiment,the operation 4862 may be implemented using the release-state selectioncircuit 2165. In an embodiment, the operation 4862 may be implementedusing the release-state selection circuit, the computing device 2175,and/or the final dosage form and stimulus exposure database 2182 (savedon the computer-readable storage medium 2180).

The modification-stimulus selection operation 4870 includes selectingthe modification-stimulus from the stimulus or the another stimulus inresponse to the selected medicament-release state. In an embodiment,modification-stimulus selection operation may be implemented using thestimulus selection circuit 2170 described in conjunction with FIG. 27.The modification-stimulus selecting operation may include at least oneadditional operation, such as the operation 4872. The operation 4872includes electronically selecting the modification-stimulus from thestimulus or the another stimulus in response to the selectedmedicament-release state, the selecting the stimulus based on anelectronically-stored database relating stimuli and medicament-releasestate of the final dosage form, a computer-implemented decision table, adigitally-maintained final dosage form transformation table, or adigital library correlating medicament-release state of the final dosageform and stimuli. In an embodiment, the stimulus selection circuit, thecomputing device 2175, and/or the final dosage form and stimulusexposure database 2182 may cooperatively implement the operation 4872.The customization operation 4820 is described in conjunction with FIG.60.

FIG. 62 illustrates an example article of manufacture 4902 foradministering medicament to an animal. The article of manufactureincludes the medicament 190A. The article of manufacture also includesan intelligent molecular means 4924 associated with the medicament in afirst release-control state. In the first release-control state, themedicament has a first bioavailability to the animal if the article ofmanufacture is administered to the animal. The intelligent molecularmeans is modifiable ex vivo by an exposure to a stimulus to associatewith the medicament in a second release-control state. In the secondrelease-control state, the medicament has a second bioavailability tothe animal if the article of manufacture is administered to the animal.

The article of manufacture 4902 includes the another medicament 190B.The article of manufacture also include another intelligent molecularmeans 4964 associated with the another medicament in another firstrelease-control state. In the another first release-control state, theanother medicament has another first bioavailability to the animal ifthe article of manufacture is administered to the animal. The anotherintelligent molecular means is modifiable ex vivo by an exposure toanother stimulus to associate with the another medicament in anothersecond release-control state. In the another second release-controlstate, the another medicament has another second bioavailability to theanimal if the article of manufacture is administered to the animal.

In an embodiment, the article of manufacture 4902 includes means 4928for indicating an exposure to the stimulus of the intelligent molecularmeans associated with a medicament in a first medicament-release state.In an embodiment, the article of manufacture includes another means 4968for indicating an exposure to the another stimulus of the anotherintelligent molecular means associated with another medicament inanother first medicament-release state. In an embodiment, the article ofmanufacture includes means 4980 for protecting the article ofmanufacture against an ex vivo environment. In an embodiment, thearticle of manufacture includes means 4990 for carrying the article ofmanufacture into the animal.

FIG. 63 illustrates an example environment 5000. The environmentincludes a final dosage form 5010 for administering medicament to theanimal 198. The final dosage form includes at least two respectiveinstances of a medicament and a substance, illustrated as instances5002.

The final dosage form 5010 includes an instance 5002.1 of a substancecarrying a medicament in a first medicament-release state. In anembodiment, the instance 5002.1 may include a large number of substanceseach respectfully carrying the medicament in a first medicament-releasestate. In an embodiment, the substance includes a gel, illustrated as ahydrogel 5002A, carrying the medicament 190A in a firstmedicament-release state. In an embodiment, the substance includes aliposome, illustrated as a liposome 5002B, carrying the medicament 190Bin a first medicament-release state. In an embodiment, the substanceincludes a nanoparticle, illustrated as nanosphere 5002C carrying themedicament 190C in a first medicament-release state. In an embodiment,the substance includes an active site of a molecule carrying themedicament in a first medicament-release state. In an embodiment, thesubstance includes a molecule carrying the medicament in a firstmedicament-release state. In an embodiment, the substance includes anintelligent molecule carrying the medicament in a firstmedicament-release state.

The medicament has a first bioavailability to the animal 198 if thefinal dosage form 5010 is administered to the animal. The substance ismodifiable ex vivo by an exposure to a first stimulus to carry themedicament in a second medicament-release state. In the secondmedicament-release state, the medicament has a second bioavailability tothe animal if the final dosage form is administered to the animal. Thesubstance is modifiable ex vivo by an exposure to a second stimulus tocarry the medicament in a third medicament-release state. In the thirdmedicament-release state, the medicament has a third bioavailability tothe animal if the final dosage form is administered to the animal.

The final dosage form 5010 includes another instance 5002.2 of anothersubstance carrying another medicament in another firstmedicament-release state. In an embodiment, the another instance 5002.2may include a large number of another substances each respectfullycarrying the another medicament in another first medicament-releasestate. In an embodiment, the another substance includes a gel,illustrated as a hydrogel 5002A, carrying the another medicament 190A inanother first medicament-release state. In an embodiment, the anothersubstance includes a liposome, illustrated as a liposome 5002B, carryingthe another medicament 190B in another first medicament-release state.In an embodiment, the another substance includes another nanoparticle,illustrated as nanosphere 5002C carrying the another medicament 190C inanother first medicament-release state. In an embodiment, the anothersubstance includes another active site of another molecule carrying theanother medicament in another first medicament-release state. In anembodiment, the another substance includes another molecule carrying theanother medicament in another first medicament-release state. In anembodiment, the another substance includes another intelligent moleculecarrying the another medicament in another first medicament-releasestate.

The another medicament has another first bioavailability to the animalif the final dosage form is administered to the animal. The anothersubstance is modifiable ex vivo by an exposure to another first stimulusto carry the another medicament in another second medicament-releasestate. In the another second medicament-release state, the anothermedicament has another second bioavailability to the animal if the finaldosage form is administered to the animal. The another substance ismodifiable ex vivo by an exposure to another second stimulus to carrythe another medicament in another third medicament-release state. In theanother third medicament-release state, the another medicament hasanother third bioavailability to the animal if the final dosage form isadministered to the animal.

In an embodiment, the substance 5002 carrying the medicament in a firstmedicament-release state includes a substance having a modifiablemedicament release characteristic and carrying the medicament in a firstmedicament-release state. In an embodiment, the substance carrying themedicament in a first medicament-release state includes a substancecarrying the medicament in an initial medicament-retention state. In anembodiment, the substance carrying the medicament in a firstmedicament-release state includes a particle carrying the medicament ina first medicament-release state. In an embodiment, the substancecarrying the medicament in a first medicament-release state includes apolymeric material carrying the medicament in a first medicament-releasestate. In an embodiment, the substance carrying the medicament in afirst medicament-release state includes a small molecule carrying themedicament in a first medicament-release state. In an embodiment, thesubstance carrying the medicament in a first medicament-release stateincludes a capsule structure carrying the medicament in a firstmedicament-release state.

In an embodiment, the medicament has a first bioavailability to theanimal includes the medicament is not bioavailable to the animal. In anembodiment, the medicament has a first bioavailability to the animalincludes the medicament is bioavailable to the animal. In an embodiment,the medicament has a second bioavailability to the animal includes themedicament is not bioavailable to the animal. In an embodiment, themedicament has a second bioavailability to the animal includes themedicament is bioavailable to the animal. In an embodiment, themedicament has a third bioavailability to the animal includes themedicament is not bioavailable to the animal. In an embodiment, themedicament has a third bioavailability to the animal includes themedicament is bioavailable to the animal.

In an embodiment, the another medicament has another firstbioavailability to the animal includes the another medicament is notbioavailable to the animal. In an embodiment, the another medicament hasanother first bioavailability to the animal includes the anothermedicament is bioavailable to the animal. In an embodiment, the anothermedicament has another second bioavailability to the animal includeswherein the another medicament is not bioavailable to the animal. In anembodiment, the another medicament has another second bioavailability tothe animal includes the another medicament is bioavailable to theanimal. In an embodiment, the another medicament has another thirdbioavailability to the animal includes the another medicament is notbioavailable to the animal. In an embodiment, the another medicament hasanother third bioavailability to the animal includes the anothermedicament is bioavailable to the animal. In an embodiment, the firstbioavailability includes a first bioavailability characteristic, thesecond bioavailability includes a second bioavailability characteristic,and the third bioavailability includes a third bioavailabilitycharacteristic.

The example environment 5000 of FIG. 63 illustrates another embodimentof the final dosage form 5010 for administering medicament to the animal198. The final dosage form includes at least two instances of amedicament and a substance, illustrated as instances 5002.

The final dosage form 5010 includes an instance 5002.1 of a substancecarrying a medicament in a medicament-retention state. The medicament issubstantially not bioavailable to the animal if the final dosage form isadministered to the animal. The substance is modifiable ex vivo by anexposure to a first stimulus to carry the medicament in a firstmedicament-release state. In the first medicament-release state, themedicament has a first bioavailability to the animal if the final dosageform is administered to the animal. The substance is modifiable ex vivoby an exposure to a second stimulus to carry the medicament in a secondmedicament-release state. In the second medicament-release state, themedicament has a second bioavailability to the animal if the finaldosage form is administered to the animal.

The final dosage form 5010 includes another instance 5002.2 of anothersubstance carrying another medicament in another medicament-retentionstate. The another medicament is substantially not bioavailable to theanimal if the final dosage form is administered to the animal 198. Theanother substance is modifiable ex vivo by an exposure to another firststimulus to carry the another medicament in another firstmedicament-release state. In the another first medicament-release state,the another medicament has another first bioavailability to the animalif the final dosage form is administered to the animal. The anothersubstance is modifiable ex vivo by an exposure to another secondstimulus to carry the another medicament in another secondmedicament-release state. In the another second medicament-releasestate, the another medicament has another second bioavailability to theanimal if the final dosage form is administered to the animal.

The following table illustrates several states of example embodiments ofthe final dosage form 5010:

TABLE 4 Example bioavailability configurations Example Configuration #1Example Configuration #2 Bioavailability Bioavailability State ofSubstance 1 Substance 2 Substance 1 Substance 2 substance (100 mg (200mg TR (100 mg (200 mg medicament medicament medicament medicament A) A)A) B) State 1 0 0 1 0 (initial) State 2 1 0 0 0 (first stimulus toSubstance 1) State 3 2 0 2 0 (second stimulus to Substance 1) State 4 01 1 1 (another first stimulus to Substance 2) State 4 0 2 1 2 (anothersecond stimulus to Substance 2) State 5 1 1 0 1 (first stimulus toSubstance 1, and another first stimulus to Substance 2) State 6 2 1 2 1(second stimulus to Substance 1, and another first stimulus to Substance2) State 7 1 2 0 2 (first stimulus to Substance 1, and another secondstimulus to Substance 2) State 8 2 2 1 2 (second stimulus to Substance1, and another second stimulus to Substance 2) 0 = medicament issubstantially not bioavailable 1 = medicament is bioavailable 2 =medicament is bioavailable in a substantially different characteristicthan in bioavailability 1

FIG. 64 illustrates an example environment 5100. The environmentincludes a final dosage form 5110 for administering medicament to theanimal 198. An element of the final dosage form is illustrated as anelement 5102.1. Another element of the final dosage includes anotherelement 5102.2 (not shown). The element and the another element may beincluded in a transport medium (not shown) of the final dosage form. Thetransport medium may include a carrier, admixture, diluent, orexcipient.

In an embodiment, the element 5102.1 of the final dosage form 5110includes an “A Dosage Portion” that is substantially similar to finaldosage form 102 described in conjunction with FIG. 1, and a “AnotherDosage Portion” that is substantially similar to final dosage form 302described in conjunction with FIG. 3. The element 5102.1 of the finaldosage form 5110 includes a medicament, illustrated in “A DosagePortion” as the medicament 190A, and a medicament, illustrated in“Another Dosage Portion” as the medicament 190B. The element 5102.1carries the medicament 190A in a first medicament-release state. In thefirst medicament-release state, the medicament 190A has a firstbioavailability to the animal 198 if the final dosage form isadministered to the animal. The element 5102.1 is modifiable ex vivo byan exposure to a first stimulus to carry the medicament 190A in a secondmedicament-release state. In the second medicament-release state, themedicament 190A has a second bioavailability to the animal if the finaldosage form is administered to the animal.

The element 5102.1 carries the medicament 190B in the “B Dosage Portion”in the first medicament-release state. In the first medicament-releasestate, the medicament 190B has a first bioavailability to the animal 198if the final dosage form is administered to the animal. The “AnotherDosage Portion” of element 5102.1 is modifiable ex vivo by an exposureto a second stimulus to carry the medicament 190B in a thirdmedicament-release state. In the third medicament-release state, themedicament has a third bioavailability to the animal if the final dosageform is administered to the animal.

In an embodiment, the element 5102.2 includes another medicament havingrelease states modifiable ex vivo in a manner substantially similar tothe element 5102.1.

FIG. 65 illustrates an example environment 5200. The environmentincludes a final dosage form 5205 and an operational flow 5220. In anembodiment, the final dosage form is substantially similar to the finaldosage form 5010 described in conjunction with FIG. 63. In anotherembodiment, the final dosage form is substantially similar to the finaldosage form 5110 described in conjunction with FIG. 64.

After a start operation, the operational flow 5210 includes acustomization operation 5220. The customization operation includestransforming the final dosage form 5205 into a selectedmedicament-release state by initiating an ex vivo exposure to amodification stimulus of the substance carrying the medicament in afirst medicament-release state or the another substance carrying theanother medicament in another first medicament-release state. Themodification stimulus is respectfully selected from the first stimulusor the second stimulus for the substance, or from the another firststimulus or the another second stimulus for the another substance. Theoperational flow includes an end operation. In an embodiment, theoperational flow 5210 may be implemented using the system 2100 describedin conjunction with FIG. 27.

In an embodiment, the customization operation 5220 may include at leastone additional operation, such as an operation 5222. The operation 5222includes transforming the final dosage form 5205 into a selectedmedicament-release state by initiating an ex vivo exposure to amodification stimulus of the substance carrying the medicament in afirst medicament-release state and the another substance carrying theanother medicament in another first medicament-release state. Themodification stimulus includes a stimulus selected from the firststimulus or the second stimulus for the substance, and another stimulusselected from the another first stimulus or the another second stimulusfor the another substance.

FIG. 66 illustrates an alternative embodiment of the operational flow5210 described in conjunction with FIG. 65. In an embodiment, theoperational flow may include at least one additional operation. The atleast one additional operation may include a treatment-order operation5250, a release-state selection operation 5260, or amodification-stimulus selection operation 5270. The treatment orderoperation includes receiving a signal indicative of a chosen medicamentbioavailability of the final dosage form. The treatment-order operationmay be implemented using the system 2100 described in conjunction withFIG. 27. The treatment-order operation may include at least oneadditional operation. The at least one additional operation may includean operation 5252 or an operation 5254. The operation 5252 includesreceiving a machine-initiated signal indicative of a chosen medicamentbioavailability of the final dosage form. In an embodiment, theoperation 5252 may be implemented using the other circuit(s) 2190 toreceive data or an email or fax indicative of the chosen medicamentbioavailability of the final dosage form. The operation 5254 includesreceiving a human-initiated signal indicative of the chosen medicamentbioavailability of the final dosage form. In an embodiment, theoperation 5254 may be implemented using the user interface 2195 of FIG.27 to receive a human-initiated input by the person 2199.

The release-state selection operation 5260 includes selecting themedicament-release state of the substance or of the another substance inresponse to the chosen medicament-bioavailability of the final dosageform. In an embodiment, the release-state selection operation may beimplemented using the release-state selection circuit 2165 of FIG. 27.In an embodiment, the release-state selection operation may beimplemented using the release-state selection circuit 2165 and a human2199 initiated input entered into the user interface 2195. In anembodiment, the release-state selection operation may include at leastone additional operation, such as an operation 5262. The operation 5262includes electronically selecting the medicament-release state of thesubstance or of the another substance in response to the chosenmedicament-bioavailability of the final dosage form. The selecting amedicament-release state is based on an electronically-stored databaserelating medicament-release state and medicament-bioavailability of thefinal dosage form, a computer-implemented decision table, adigitally-maintained final dosage form transformation table, or adigital library correlating medicament-release state andmedicament-bioavailability of the final dosage form. In an embodiment,the operation 5262 may be implemented using the release-state selectioncircuit 2165. In an embodiment, the operation 5262 may be implementedusing the release-state selection circuit, the computing device 2175,and/or the final dosage form and stimulus exposure database 2182 (savedon the computer-readable storage medium 2180).

The modification-stimulus selection operation 5270 includes selectingthe modification-stimulus from the first stimulus, the second stimulus,the another first stimulus or the another second stimulus in response tothe selected medicament-release state. In an embodiment,modification-stimulus selection operation may be implemented using thestimulus selection circuit 2170 described in conjunction with FIG. 27.In an embodiment, the stimulus selection circuit, the computing device2175, and/or the final dosage form and stimulus exposure database 2182may cooperatively implement the operation 5270. Themodification-stimulus selecting operation may include at least oneadditional operation, such as the operation 5272. The operation 5272includes electronically selecting the modification stimulus in responseto the selected medicament-release state. The selecting the modificationstimulus is based on an electronically-stored database relating stimuliand medicament-release state of the final dosage form, acomputer-implemented decision table, a digitally-maintained final dosageform transformation table, or a digital library correlatingmedicament-release state of the final dosage form and stimuli. Thecustomization operation 5220 is described in conjunction with FIG. 65.

FIG. 67 illustrates an example article of manufacture 5702 foradministering medicament to an animal. The article of manufactureincludes a medicament 190A. The article of manufacture also includesintelligent molecular 5724 means associated with the medicament in afirst medicament-release state wherein the medicament has a firstbioavailability to the animal if the article of manufacture isadministered to the animal. The intelligent molecular means ismodifiable ex vivo by an exposure to a first stimulus to carry themedicament in a second medicament-release state. In the secondmedicament-release state, the medicament has a second bioavailability tothe animal if the article of manufacture is administered to the animal.The intelligent molecular means is modifiable ex vivo by an exposure toa second stimulus to carry the medicament in a third medicament-releasestate. In the third medicament-release state, the medicament has a thirdbioavailability to the animal if the article of manufacture isadministered to the animal.

The article of manufacture includes another medicament 190B. The articleof manufacture also includes another intelligent molecular means 5764associated with the another medicament in another firstmedicament-release state wherein the another medicament has anotherfirst bioavailability to the animal if the article of manufacture isadministered to the animal. The another intelligent molecular means ismodifiable ex vivo by an exposure to another first stimulus to carry theanother medicament in another second medicament-release state. Inanother second medicament-release state, the another medicament hasanother second bioavailability to the animal if the article ofmanufacture is administered to the animal. The another intelligentmolecular means is modifiable ex vivo by an exposure to another secondstimulus to carry the another medicament in another thirdmedicament-release state. In another third medicament-release state, theanother medicament has another third bioavailability to the animal ifthe article of manufacture is administered to the animal.

All references cited herein are hereby incorporated by reference intheir entirety or to the extent their subject matter is not inconsistentherewith.

In some embodiments, “configured” includes at least one of designed, setup, shaped, implemented, constructed, or adapted for at least one of aparticular purpose, application, or function.

It will be understood that, in general, terms used herein, andespecially in the appended claims, are generally intended as “open”terms (e.g., the term “including” should be interpreted as “includingbut not limited to,” the term “having” should be interpreted as “havingat least,” the term “includes” should be interpreted as “includes but isnot limited to,” etc.). It will be further understood that if a specificnumber of an introduced claim recitation is intended, such an intentwill be explicitly recited in the claim, and in the absence of suchrecitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage ofintroductory phrases such as “at least one” or “one or more” tointroduce claim recitations. However, the use of such phrases should notbe construed to imply that the introduction of a claim recitation by theindefinite articles “a” or “an” limits any particular claim containingsuch introduced claim recitation to inventions containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a receiver” should typically be interpreted to mean “atleast one receiver”); the same holds true for the use of definitearticles used to introduce claim recitations. In addition, even if aspecific number of an introduced claim recitation is explicitly recited,it will be recognized that such recitation should typically beinterpreted to mean at least the recited number (e.g., the barerecitation of “at least two chambers,” or “a plurality of chambers,”without other modifiers, typically means at least two chambers).

Use of “Start,” “End” or “Stop” blocks in the block diagrams is notintended to indicate a limitation on the beginning or end of anyfunctions in the diagram. Such flowcharts or diagrams may beincorporated into other flowcharts or diagrams where additionalfunctions are performed before or after the functions shown in thediagrams of this application.

In those instances where a phrase such as “at least one of A, B, and C,”“at least one of A, B, or C,” or “an [item] selected from the groupconsisting of A, B, and C,” is used, in general such a construction isintended to be disjunctive (e.g., any of these phrases would include butnot be limited to systems that have A alone, B alone, C alone, A and Btogether, A and C together, B and C together, or A, B, and C together,and may further include more than one of A, B, or C, such as A₁, A₂, andC together, A, B₁, B₂, C₁, and C₂ together, or B₁ and B₂ together). Itwill be further understood that virtually any disjunctive word or phrasepresenting two or more alternative terms, whether in the description,claims, or drawings, should be understood to contemplate thepossibilities of including one of the terms, either of the terms, orboth terms. For example, the phrase “A or B” will be understood toinclude the possibilities of “A” or “B” or “A and B.”

The herein described aspects depict different components containedwithin, or connected with, different other components. It is to beunderstood that such depicted architectures are merely examples, andthat in fact many other architectures can be implemented which achievethe same functionality. In a conceptual sense, any arrangement ofcomponents to achieve the same functionality is effectively “associated”such that the desired functionality is achieved. Hence, any twocomponents herein combined to achieve a particular functionality can beseen as “associated with” each other such that the desired functionalityis achieved, irrespective of architectures or intermedial components.Likewise, any two components so associated can also be viewed as being“operably connected,” or “operably coupled,” to each other to achievethe desired functionality. Any two components capable of being soassociated can also be viewed as being “operably couplable” to eachother to achieve the desired functionality. Specific examples ofoperably couplable include but are not limited to physically mateable orphysically interacting components or wirelessly interactable orwirelessly interacting components.

With respect to the appended claims the recited operations therein maygenerally be performed in any order. Also, although various operationalflows are presented in a sequence(s), it should be understood that thevarious operations may be performed in other orders than those which areillustrated, or may be performed concurrently. Examples of suchalternate orderings may include overlapping, interleaved, interrupted,reordered, incremental, preparatory, supplemental, simultaneous,reverse, or other variant orderings, unless context dictates otherwise.Furthermore, terms like “responsive to,” “related to,” or otherpast-tense adjectives are generally not intended to exclude suchvariants, unless context dictates otherwise.

While various aspects and embodiments have been disclosed herein, thevarious aspects and embodiments are for purposes of illustration and arenot intended to be limiting, with the true scope and spirit beingindicated by the following claims.

What is claimed is:
 1. A final dosage form for administering medicamentto an animal, the final dosage form comprises: a dosage portion having amedicament; and a release element in a first medicament-release statewherein the medicament has a first bioavailability to the animal if thefinal dosage form is administered to the animal in the firstmedicament-release state, the release element modifiable ex vivo to asecond medicament-release state by an exposure to a stimulus, whereinthe medicament has a second bioavailability to the animal if the finaldosage form is administered to the animal in the secondmedicament-release state; and another dosage portion having anothermedicament; and another release element in another firstmedicament-release state wherein the another medicament has anotherfirst bioavailability to the animal if the final dosage form isadministered to the animal in the another first medicament-releasestate, the another release element modifiable ex vivo to another secondmedicament-release state by an exposure to another stimulus, wherein theanother medicament has another second bioavailability to the animal ifthe final dosage form is administered to the animal in the anothersecond medicament-release state.
 2. The final dosage form of claim 1,wherein the first medicament-release state wherein the medicament has afirst bioavailability to the animal includes: a first medicament-releasestate wherein the medicament is not bioavailable to the animal.
 3. Thefinal dosage form of claim 1, wherein the first medicament-release statewherein the medicament has a first bioavailability to the animalincludes: a first medicament-release state wherein the medicament isbioavailable to the animal.
 4. The final dosage form of claim 1, whereinthe second medicament-release state wherein the medicament has a secondbioavailability to the animal includes: a second medicament-releasestate wherein the medicament is not bioavailable to the animal.
 5. Thefinal dosage form of claim 1, wherein the second medicament-releasestate wherein the medicament has a second bioavailability to the animalincludes: a second medicament-release state wherein the medicament isbioavailable to the animal.
 6. The final dosage form of claim 1, whereinthe another first medicament-release state wherein the anothermedicament has another first bioavailability to the animal includes:another first medicament-release state wherein the another medicament isnot bioavailable to the animal.
 7. The final dosage form of claim 1,wherein the another first medicament-release state wherein the anothermedicament has another first bioavailability to the animal includes:another first medicament-release state wherein the another medicament isbioavailable to the animal.
 8. The final dosage form of claim 1, whereinthe another second medicament-release state wherein the anothermedicament has another second bioavailability to the animal includes:another second medicament-release state wherein the another medicamentis not bioavailable to the animal.
 9. The final dosage form of claim 1,wherein the another second medicament-release state wherein the anothermedicament has another second bioavailability to the animal includes:another second medicament-release state wherein the another medicamentis bioavailable to the animal.
 10. The final dosage form of claim 1,wherein the first bioavailability to the animal includes a firstbioavailability characteristic and the second bioavailability to theanimal includes a second bioavailability characteristic.
 11. The finaldosage form of claim 1, wherein the stimulus includes: at least one of amechanical stimulus, a non-ionizing radiation stimulus, an ionizingradiation stimulus, a chemical stimulus, an acoustic stimulus, anultrasound stimulus, a radio wave stimulus, a microwave stimulus, alight wave stimulus, or a thermal stimulus.
 12. A final dosage form foradministering a medicament to an animal, the final dosage formcomprises: a dosage portion having: a medicament; a release element in amedicament-holding state wherein the medicament is substantially notbioavailable to the animal if the final dosage form is administered tothe animal in the medicament-holding state, the release elementmodifiable ex vivo to a medicament-discharging state by an exposure to astimulus wherein the medicament is bioavailable to the animal if thefinal dosage form is administered to the animal in themedicament-discharging state; and another dosage portion having anothermedicament; another release element in another medicament-holding statewherein the another medicament is substantially not bioavailable to theanimal if the final dosage form is administered to the animal in theanother medicament-holding state, the another release element modifiableex vivo to another medicament-discharge state by an exposure to anotherstimulus wherein the another medicament is bioavailable to the animal ifthe final dosage form is administered to the animal in the anothermedicament-discharge state.
 13. The final dosage form of claim 12,further comprising: an outer layer carrying the dosage portion and theanother dosage portion.
 14. A method of modifying medicamentbioavailability of a final dosage form for administering medicament toan animal, wherein the final dosage form includes a dosage portionhaving a medicament; and a release element in a first medicament-releasestate wherein the medicament has a first bioavailability to the animalif the final dosage form is administered to the animal in the firstmedicament-release state, the release element modifiable ex vivo to asecond medicament-release state by an exposure to a stimulus, whereinthe medicament has a second bioavailability to the animal if the finaldosage form is administered to the animal in the secondmedicament-release state; and another dosage portion having anothermedicament; and another release element in another firstmedicament-release state wherein the another medicament has anotherfirst bioavailability to the animal if the final dosage form isadministered to the animal in the another first medicament-releasestate, the another release element modifiable ex vivo to another secondmedicament-release state by an exposure to another stimulus, wherein theanother medicament has another second bioavailability to the animal ifthe final dosage form is administered to the animal in the anothersecond medicament-release state; the method comprising: transforming thefinal dosage form into a selected medicament release profile byinitiating an ex vivo exposure of the release element or the anotherrelease element to a modification stimulus respectfully selected fromthe stimulus or the another stimulus.
 15. The method of claim 14,further comprising: receiving a signal indicative of a chosen medicamentbioavailability of the final dosage form.
 16. The method of claim 15,wherein receiving signal indicative of a chosen medicamentbioavailability of the final dosage form includes: receiving amachine-initiated signal indicative indication of a chosen medicamentbioavailability of the final dosage form.
 17. The method of claim 15,wherein receiving signal indicative of a chosen medicamentbioavailability of the final dosage form includes: receiving ahuman-initiated signal indicative of a chosen medicament bioavailabilityof the final dosage form.
 18. The method of claim 14, furthercomprising: selecting a medicament-release state of the release elementor of the another release element in response to the chosenmedicament-bioavailability of the final dosage form.
 19. The method ofclaim 18, wherein the selecting a medicament-release state of therelease element or of the another release element in response to theselected medicament-bioavailability of the final dosage form includes:electronically selecting a medicament-release state of the releaseelement or of the another release element in response to the selectedmedicament-bioavailability of the final dosage form, the selecting amedicament-release state based on an electronically-stored databaserelating medicament-release state and medicament-bioavailability of thefinal dosage form, a computer-implemented decision table, adigitally-maintained final dosage form transformation table, or adigital library correlating medicament-release state andmedicament-bioavailability of the final dosage form.
 20. The method ofclaim 14, further comprising: selecting the stimulus for initiation fromthe stimulus or the another stimulus in response to the selectedmedicament-release state.
 21. The method of claim 20, wherein theselecting the modification stimulus from the stimulus or the anotherstimulus in response to the selected medicament-release state includes:electronically selecting the modification stimulus from the stimulus orthe another stimulus in response to the selected medicament-releasestate, the selecting the stimulus based on an electronically-storeddatabase relating stimuli and medicament-release state of the finaldosage form, a computer-implemented decision table, adigitally-maintained final dosage form transformation table, or adigital library correlating medicament-release state of the final dosageform and stimuli.
 22. The method of claim 14, wherein the transformingthe final dosage form into a selected medicament release profile byinitiating an ex vivo exposure of the release element or the anotherrelease element to a modification stimulus respectfully selected fromthe stimulus or the another stimulus includes: transforming the finaldosage form into a selected medicament release profile by initiating anex vivo exposure of the release element and the another release elementto the stimulus and the another stimulus.
 23. An article of manufacturecomprising: a final dosage form for administering medicament to ananimal, the final dosage form including a dosage portion having amedicament; and a release element in a first medicament-release statewherein the medicament has a first bioavailability to the animal if thefinal dosage form is administered to the animal in the firstmedicament-release state, the release element modifiable ex vivo to asecond medicament-release state by an exposure to a stimulus, whereinthe medicament has a second bioavailability to the animal if the finaldosage form is administered to the animal in the secondmedicament-release state; and another dosage portion having anothermedicament another release element in another first medicament-releasestate wherein the another medicament has another first bioavailabilityto the animal if the final dosage form is administered to the animal inthe another first medicament-release state, the another release elementmodifiable ex vivo to another second medicament-release state by anexposure to another stimulus, wherein the another medicament has anothersecond bioavailability to the animal if the final dosage form isadministered to the animal in the another second medicament-releasestate; and instructions specifying an ex vivo exposure of the releaseelement to the stimulus or an ex vivo exposure of the another releaseelement to the another stimulus which when implemented respectfullytransform the release element to the second medicament-release state orthe another release element to the another second medicament-releasestate.
 24. An article of manufacture for administering medicament to ananimal, the article comprising: a medicament; means for medicamentrelease control in a first state wherein the medicament has a firstbioavailability to the animal if the article of manufacture isadministered to the animal, the means for medicament release controlmodifiable ex vivo to a second state by an exposure to a stimulus,wherein the medicament has a second bioavailability to the animal if thearticle of manufacture is administered to the animal; anothermedicament; and another means for medicament release control in anotherfirst state wherein the another medicament has another firstbioavailability to the animal if the article of manufacture isadministered to the animal, the another means for medicament releasecontrol modifiable ex vivo to another second state by an exposure toanother stimulus, wherein the another medicament has another secondbioavailability to the animal if the article of manufacture isadministered to the animal.